Picolinamides as fungicides

ABSTRACT

This disclosure relates to picolinamides of Formula I and their use as fungicides.

CROSS REFERENCE TO RELATED APPLICATION

This is a national phase entry under 35 U.S.C. § 371 of international patent application PCT/US2019/021263, filed on Mar. 8, 2019 and published in English as international patent publication WO2019173665 on Sep. 12, 2019, which claims priority to the benefit of of U.S. Provisional Patent Application Ser. No. 62/640,424 filed Mar. 8, 2018 and U.S. Provisional Patent Application Ser. No. 62/640,434 filed Mar. 8, 2018 the disclosure of which is hereby incorporated by reference in its entirety.

BACKGROUND & SUMMARY

Fungicides are compounds, of natural or synthetic origin, which act to protect and/or cure plants against damage caused by agriculturally relevant fungi. Generally, no single fungicide is useful in all situations. Consequently, research is ongoing to produce fungicides that may have better performance, are easier to use, and cost less.

The present disclosure relates to picolinamides and their use as fungicides. The compounds of the present disclosure may offer protection against ascomycetes, basidiomycetes, deuteromycetes and oomycetes.

One embodiment of the present disclosure may include compounds of Formula I:

wherein:

Q is

X is hydrogen or C(O)R₄;

Y is hydrogen or C(O)R₄;

Z is N or N⁺→O⁻ and W is O or S;

R₁ is hydrogen or alkyl, substituted with 0, 1 or multiple R₇;

R₂ is methyl;

R₃ is chosen from alkyl, aryl or heteroaryl, each optionally substituted with 0, 1 or multiple R₇;

R₄ is chosen from alkoxy or benzyloxy, each optionally substituted with 0, 1, or multiple R₇;

R₅ is chosen from hydrogen, alkoxy, or halo, each optionally substituted with 0, 1, or multiple R₇;

R₆ is chosen from hydrogen, —C(O)R₈, or —CH₂OC(O)R₈;

R₇ is chosen from hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkynyl, alkoxy, cyano, or heterocyclyl, each optionally substituted with 0, 1, or multiple R₉;

R₈ is chosen from alkyl, alkoxy, or aryl, each optionally substituted with 0, 1, or multiple R₇;

R₉ is chosen from hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkoxy, or heterocyclyl; and

R₁₀ is chosen from hydrogen or alkyl, each substituted with 0, 1 or multiple R₇.

Another embodiment of the present disclosure may include a fungicidal composition for the control or prevention of fungal attack comprising the compounds described above and a phytologically acceptable carrier material.

Yet another embodiment of the present disclosure may include a method for the control or prevention of fungal attack on a plant, the method including the steps of applying a fungicidally effective amount of one or more of the compounds described above to at least one of the fungus, the plant, and an area adjacent to the plant.

It will be understood by those skilled in the art that the following terms may include generic “R”-groups within their definitions, e.g., “the term alkoxy refers to an —OR substituent”. It is also understood that within the definitions for the following terms, these “R” groups are included for illustration purposes and should not be construed as limiting or being limited by substitutions about Formula I.

The term “alkyl” refers to a branched, unbranched, or saturated cyclic carbon chain, including, but not limited to, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, tertiary butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like.

The term “alkenyl” refers to a branched, unbranched or cyclic carbon chain containing one or more double bonds including, but not limited to, ethenyl, propenyl, butenyl, isopropenyl, isobutenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, and the like.

The terms “aryl” and “Ar” refer to any aromatic ring, mono- or bi-cyclic, containing 0 heteroatoms.

The term “heterocyclyl” refers to any aromatic or non-aromatic ring, mono- or bi-cyclic, containing one or more heteroatoms

The term “alkoxy” refers to an —OR substituent.

The term “acyloxy” refers to an —OC(O)R substituent.

The term “cyano” refers to a —C≡N substituent.

The term “hydroxyl” refers to a —OH substituent.

The term “amino” refers to an —N(R)₂ substituent.

The term “arylalkoxy” refers to —O(CH₂)_(n)Ar where n is an integer selected from the list 1, 2, 3, 4, 5, or 6.

The term “haloalkoxy” refers to an —OR—X substituent, wherein X is Cl, F, Br, or I, or any combination thereof.

The term “haloalkyl” refers to an alkyl, which is substituted with Cl, F, I, or Br or any combination thereof.

The term “halogen” or “halo” refers to one or more halogen atoms, defined as F, Cl, Br, and I.

The term “nitro” refers to a —NO₂ substituent.

The term thioalkyl refers to a —SR substituent.

Throughout the disclosure, reference to the compounds of Formula I is read as also including all stereoisomers, for example diastereomers, enantiomers, and mixtures thereof. In another embodiment, Formula (I) is read as also including salts or hydrates thereof. Exemplary salts include, but are not limited to: hydrochloride, hydrobromide, hydroiodide, trifluoroacetate, and trifluoromethane sulfonate.

It is also understood by those skilled in the art that additional substitution is allowable, unless otherwise noted, as long as the rules of chemical bonding and strain energy are satisfied and the product still exhibits fungicidal activity.

Another embodiment of the present disclosure is a use of a compound of Formula I, for protection of a plant against attack by a phytopathogenic organism or the treatment of a plant infested by a phytopathogenic organism, comprising the application of a compound of Formula I, or a composition comprising the compound to soil, a plant, a part of a plant, foliage, and/or roots.

Additionally, another embodiment of the present disclosure is a composition useful for protecting a plant against attack by a phytopathogenic organism and/or treatment of a plant infested by a phytopathogenic organism comprising a compound of Formula I and a phytologically acceptable carrier material.

DETAILED DESCRIPTION

The compounds of the present disclosure may be applied by any of a variety of known techniques, either as the compounds or as formulations comprising the compounds. For example, the compounds may be applied to the roots or foliage of plants for the control of various fungi, without damaging the commercial value of the plants. The materials may be applied in the form of any of the generally used formulation types, for example, as solutions, dusts, wettable powders, flowable concentrate, or emulsifiable concentrates.

Preferably, the compounds of the present disclosure are applied in the form of a formulation, comprising one or more of the compounds of Formula I with a phytologically acceptable carrier. Concentrated formulations may be dispersed in water, or other liquids, for application, or formulations may be dust-like or granular, which may then be applied without further treatment. The formulations can be prepared according to procedures that are conventional in the agricultural chemical art.

The present disclosure contemplates all vehicles by which one or more of the compounds may be formulated for delivery and used as a fungicide. Typically, formulations are applied as aqueous suspensions or emulsions. Such suspensions or emulsions may be produced from water-soluble, water-suspendible, or emulsifiable formulations which are solids, usually known as wettable powders; or liquids, usually known as emulsifiable concentrates, aqueous suspensions, or suspension concentrates. As will be readily appreciated, any material to which these compounds may be added may be used, provided it yields the desired utility without significant interference with the activity of these compounds as antifungal agents.

Wettable powders, which may be compacted to form water-dispersible granules, comprise an intimate mixture of one or more of the compounds of Formula I, an inert carrier and surfactants. The concentration of the compound in the wettable powder may be from about 10 percent to about 90 percent by weight based on the total weight of the wettable powder, more preferably about 25 weight percent to about 75 weight percent. In the preparation of wettable powder formulations, the compounds may be compounded with any finely divided solid, such as prophyllite, talc, chalk, gypsum, Fuller's earth, bentonite, attapulgite, starch, casein, gluten, montmorillonite clays, diatomaceous earths, purified silicates or the like. In such operations, the finely divided carrier and surfactants are typically blended with the compound(s) and milled.

Emulsifiable concentrates of the compounds of Formula I may comprise a convenient concentration, such as from about 1 weight percent to about 50 weight percent of the compound, in a suitable liquid, based on the total weight of the concentrate. The compounds may be dissolved in an inert carrier, which is either a water-miscible solvent or a mixture of water-immiscible organic solvents, and emulsifiers. The concentrates may be diluted with water and oil to form spray mixtures in the form of oil-in-water emulsions. Useful organic solvents include aromatics, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, for example, terpenic solvents, including rosin derivatives, aliphatic ketones, such as cyclohexanone, and complex alcohols, such as 2-ethoxyethanol.

Emulsifiers which may be advantageously employed herein may be readily determined by those skilled in the art and include various nonionic, anionic, cationic and amphoteric emulsifiers, or a blend of two or more emulsifiers. Examples of nonionic emulsifiers useful in preparing the emulsifiable concentrates include the polyalkylene glycol ethers and condensation products of alkyl and aryl phenols, aliphatic alcohols, aliphatic amines or fatty acids with ethylene oxide, propylene oxides such as the ethoxylated alkyl phenols and carboxylic esters solubilized with the polyol or polyoxyalkylene. Cationic emulsifiers include quaternary ammonium compounds and fatty amine salts. Anionic emulsifiers include the oilsoluble salts (e.g., calcium) of alkylaryl sulphonic acids, oil-soluble salts or sulfated polyglycol ethers and appropriate salts of phosphated-polyglycol ether.

Representative organic liquids which may be employed in preparing the emulsifiable concentrates of the compounds of the present disclosure are the aromatic liquids such as xylene, propyl benzene fractions; or mixed naphthalene fractions, mineral oils, substituted aromatic organic liquids such as dioctyl phthalate; kerosene; dialkyl amides of various fatty acids, particularly the dimethyl amides of fatty glycols and glycol derivatives such as the n-butyl ether, ethyl ether or methyl ether of diethylene glycol, the methyl ether of triethylene glycol, petroleum fractions or hydrocarbons such as mineral oil, aromatic solvents, paraffinic oils, and the like; vegetable oils such as soy bean oil, rape seed oil, olive oil, castor oil, sunflower seed oil, coconut oil, corn oil, cotton seed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and the like; esters of the above vegetable oils; and the like. Mixtures of two or more organic liquids may also be employed in the preparation of the emulsifiable concentrate. Organic liquids include xylene, and propyl benzene fractions, with xylene being most preferred in some cases. Surface-active dispersing agents are typically employed in liquid formulations and in an amount of from 0.1 to 20 percent by weight based on the combined weight of the dispersing agent with one or more of the compounds. The formulations can also contain other compatible additives, for example, plant growth regulators and other biologically active compounds used in agriculture.

Aqueous suspensions comprise suspensions of one or more water-insoluble compounds of Formula I, dispersed in an aqueous vehicle at a concentration in the range from about 1 to about 50 weight percent, based on the total weight of the aqueous suspension. Suspensions are prepared by finely grinding one or more of the compounds, and vigorously mixing the ground material into a vehicle comprised of water and surfactants chosen from the same types discussed above. Other components, such as inorganic salts and synthetic or natural gums, may also be added to increase the density and viscosity of the aqueous vehicle.

The compounds of Formula I can also be applied as granular formulations, which are particularly useful for applications to the soil. Granular formulations generally contain from about 0.5 to about 10 weight percent, based on the total weight of the granular formulation of the compound(s), dispersed in an inert carrier which consists entirely or in large part of coarsely divided inert material such as attapulgite, bentonite, diatomite, clay or a similar inexpensive substance. Such formulations are usually prepared by dissolving the compounds in a suitable solvent and applying it to a granular carrier which has been preformed to the appropriate particle size, in the range of from about 0.5 to about 3 mm. A suitable solvent is a solvent in which the compound is substantially or completely soluble. Such formulations may also be prepared by making a dough or paste of the carrier and the compound and solvent, and crushing and drying to obtain the desired granular particle.

Dusts containing the compounds of Formula I may be prepared by intimately mixing one or more of the compounds in powdered form with a suitable dusty agricultural carrier, such as, for example, kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1 to about 10 weight percent of the compounds, based on the total weight of the dust.

The formulations may additionally contain adjuvant surfactants to enhance deposition, wetting, and penetration of the compounds onto the target crop and organism. These adjuvant surfactants may optionally be employed as a component of the formulation or as a tank mix. The amount of adjuvant surfactant will typically vary from 0.01 to 1.0 percent by volume, based on a spray-volume of water, preferably 0.05 to 0.5 volume percent. Suitable adjuvant surfactants include, but are not limited to ethoxylated nonyl phenols, ethoxylated synthetic or natural alcohols, salts of the esters or sulphosuccinic acids, ethoxylated organosilicones, ethoxylated fatty amines, blends of surfactants with mineral or vegetable oils, crop oil concentrate (mineral oil (85%)+emulsifiers (15%)); nonylphenol ethoxylate; benzylcocoalkyldimethyl quaternary ammonium salt; blend of petroleum hydrocarbon, alkyl esters, organic acid, and anionic surfactant; C₉-C₁₁ alkylpolyglycoside; phosphated alcohol ethoxylate; natural primary alcohol (C₁₂-C₁₆) ethoxylate; di-sec-butylphenol EO-PO block copolymer; polysiloxane-methyl cap; nonylphenol ethoxylate+ urea ammonium nitrate; emulsified methylated seed oil; tridecyl alcohol (synthetic) ethoxylate (8EO); tallow amine ethoxylate (15 EO); PEG(400) dioleate-99. The formulations may also include oil-in-water emulsions such as those disclosed in U.S. patent application Ser. No. 11/495,228, the disclosure of which is expressly incorporated by reference herein.

The formulations may optionally include combinations that contain other pesticidal compounds. Such additional pesticidal compounds may be fungicides, insecticides, herbicides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds. Accordingly, in such embodiments, the other pesticidal compound is employed as a supplemental toxicant for the same or for a different pesticidal use. The compounds of Formula I and the pesticidal compound in the combination can generally be present in a weight ratio of from 1:100 to 100:1.

The compounds of the present disclosure may also be combined with other fungicides to form fungicidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the present disclosure are often applied in conjunction with one or more other fungicides to control a wider variety of undesirable diseases. When used in conjunction with other fungicide(s), the presently claimed compounds may be formulated with the other fungicide(s), tank-mixed with the other fungicide(s) or applied sequentially with the other fungicide(s). Such other fungicides may include 2-(thiocyanatomethylthio)-benzothiazole, 2-phenylphenol, 8-hydroxyquinoline sulfate, ametoctradin, aminopyrifen, amisulbrom, antimycin, Ampelomyces quisqualis, azaconazole, Bacillus subtilis, Bacillus subtilis strain QST713, benalaxyl, benomyl, benthiavalicarb-isopropyl, benzovindiflupyr, benzylaminobenzene-sulfonate (BABS) salt, bicarbonates, biphenyl, bismerthiazol, bitertanol, bixafen, blasticidin-S, borax, Bordeaux mixture, boscalid, bromuconazole, bupirimate, calcium polysulfide, captafol, captan, carbendazim, carboxin, carpropamid, carvone, chlazafenone, chloroneb, chlorothalonil, chlozolinate, Coniothyrium minitans, copper hydroxide, copper octanoate, copper oxychloride, copper sulfate, copper sulfate (tribasic), cuprous oxide, cyazofamid, cyflufenamid, cymoxanil, cyproconazole, cyprodinil, dazomet, debacarb, diammonium ethylenebis-(dithiocarbamate), dichlofluanid, dichlorophen, diclocymet, diclomezine, dichloran, diethofencarb, difenoconazole, difenzoquat ion, diflumetorim, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinobuton, dinocap, diphenylamine, dithianon, dodemorph, dodemorph acetate, dodine, dodine free base, edifenphos, enestrobin, enestroburin, epoxiconazole, ethaboxam, ethoxyquin, etridiazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fenpyrazamine, fentin, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, fluindapyr, flumorph, fluopicolide, fluopyram, fluoroimide, fluoxapiprolin, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutianil, flutolanil, flutriafol, fluxapyroxad, folpet, formaldehyde, fosetyl, fosetyl-aluminium, fuberidazole, furalaxyl, furametpyr, guazatine, guazatine acetates, GY-81, hexachlorobenzene, hexaconazole, hymexazol, imazalil, imazalil sulfate, imibenconazole, iminoctadine, iminoctadine triacetate, iminoctadine tris(albesilate), inpyrfluxam, iodocarb, ipconazole, ipfenpyrazolone, iprobenfos, iprodione, iprovalicarb, isofetamide, isoflucypram, isoprothiolane, isopyrazam, isotianil, kasugamycin, kasugamycin hydrochloride hydrate, kresoxium-methyl, laminarin, mancopper, mancozeb, mandipropamid, maneb, mefenoxam, mepanipyrim, mepronil, meptyl-dinocap, mercuric chloride, mercuric oxide, mercurous chloride, metalaxyl, metalaxyl-M, metam, metam-ammonium, metam-potassium, metam-sodium, metconazole, methasulfocarb, methyl iodide, methyl isothiocyanate, metiram, metominostrobin, metrafenone, mildiomycin, myclobutanil, nabam, nitrothal-isopropyl, nuarimol, octhilinone, ofurace, oleic acid (fatty acids), orysastrobin, oxadixyl, oxathiapiprolin, oxine-copper, oxpoconazole fumarate, oxycarboxin, pefurazoate, penconazole, pencycuron, penflufen, pentachlorophenol, pentachlorophenyl laurate, penthiopyrad, phenylmercury acetate, phosphonic acid, phthalide, picoxystrobin, polyoxin B, polyoxins, polyoxorim, potassium bicarbonate, potassium hydroxyquinoline sulfate, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazole, propineb, proquinazid, prothioconazole, pydiflumetofen, pyrametostrobin, pyraoxystrobin, pyraclostrobin, pyraziflumid, pyrazophos, pyribencarb, pyributicarb, pyrifenox, pyrimethanil, pyriofenone, pyroquilon, quinoclamine, quinoxyfen, quintozene, Reynoutria sachalinensis extract, sedaxane, silthiofam, simeconazole, sodium 2-phenylphenoxide, sodium bicarbonate, sodium pentachlorophenoxide, spiroxamine, sulfur, SYP-Z048, tar oils, tebuconazole, tebufloquin, tecnazene, tetraconazole, thiabendazole, thifluzamide, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazoxide, tricyclazole, tridemorph, trifloxystrobin, triflumizole, triforine, triticonazole, validamycin, valifenalate, valiphenal, vinclozolin, zineb, ziram, zoxamide, Candida oleophila, Fusarium oxysporum, Gliocladium spp., Phlebiopsis gigantea, Streptomyces griseoviridis, Trichoderma spp., (RS)-N-(3,5-dichlorophenyl)-2-(methoxymethyl)-succinimide, 1,2-dichloropropane, 1,3-dichloro-1,1,3,3-tetrafluoroacetone hydrate, 1-chloro-2,4-dinitronaphthalene, 1-chloro-2-nitropropane, 2-(2-heptadecyl-2-imidazolin-1-yl)ethanol, 2,3-dihydro-5-phenyl-1,4-dithi-ine 1,1,4,4-tetraoxide, 2-methoxyethylmercury acetate, 2-methoxyethylmercury chloride, 2-methoxyethylmercury silicate, 3-(4-chlorophenyl)-5-methylrhodanine, 4-(2-nitroprop-1-enyl)phenyl thiocyanateme, ampropylfos, anilazine, azithiram, barium polysulfide, Bayer 32394, benodanil, benquinox, bentaluron, benzamacril; benzamacril-isobutyl, benzamorf, binapacryl, bis(methylmercury) sulfate, bis(tributyltin) oxide, buthiobate, cadmium calcium copper zinc chromate sulfate, carbamorph, CECA, chlobenthiazone, chloraniformethan, chlorfenazole, chlorquinox, climbazole, copper bis(3-phenylsalicylate), copper zinc chromate, coumoxystrobin, cufraneb, cupric hydrazinium sulfate, cuprobam, cyclafuramid, cypendazole, cyprofuram, decafentin, dichlobentiazox, dichlone, dichlozoline, diclobutrazol, dimethirimol, dinocton, dinosulfon, dinoterbon, dipymetitrone, dipyrithione, ditalimfos, dodicin, drazoxolon, EBP, enoxastrobin, ESBP, etaconazole, etem, ethirim, fenaminstrobin, fenaminosulf, fenapanil, fenitropan, fenpicoxamid, florylpicoxamid, flufenoxystrobin, fluopimomide, fluotrimazole, furcarbanil, furconazole, furconazole-cis, furmecyclox, furophanate, glyodine, griseofulvin, halacrinate, Hercules 3944, hexylthiofos, ICIA0858, ipfentrifluconazole, ipflufenoquin, isopamphos, isovaledione, mandestrobin, mebenil, mecarbinzid, mefentrifluconazole, metazoxolon, methfuroxam, methylmercury dicyandiamide, metsulfovax, metyltetraprole, milneb, mucochloric anhydride, myclozolin, N-3,5-dichlorophenyl-succinimide, N-3-nitrophenylitaconimide, natamycin, N-ethylmercurio-4-toluenesulfonanilide, nickel bis(dimethyldithiocarbamate), OCH, phenylmercury dimethyldithiocarbamate, phenylmercury nitrate, phosdiphen, prothiocarb; prothiocarb hydrochloride, pyracarbolid, pyrapropoyne, pyridachlometyl, pyridinitril, pyrisoxazole, pyroxychlor, pyroxyfur, quinacetol; quinacetol sulfate, quinazamid, quinconazole, quinofumelin, rabenzazole, salicylanilide, SSF-109, sultropen, tecoram, thiadifluor, thicyofen, thiochlorfenphim, thiophanate, thioquinox, tioxymid, triamiphos, triarimol, triazbutil, trichlamide, triclopyricarb, triflumezopyrim, urbacid, zarilamid, and any combinations thereof.

Additionally, the compounds described herein may be combined with other pesticides, including insecticides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds to form pesticidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the present disclosure may be applied in conjunction with one or more other pesticides to control a wider variety of undesirable pests. When used in conjunction with other pesticides, the presently claimed compounds may be formulated with the other pesticide(s), tank-mixed with the other pesticide(s) or applied sequentially with the other pesticide(s). Typical insecticides include, but are not limited to: 1,2-dichloropropane, abamectin, acephate, acetamiprid, acethion, acetoprole, acrinathrin, acrylonitrile, acynonapyr, afidopyropen, alanycarb, aldicarb, aldoxycarb, aldrin, allethrin, allosamidin, allyxycarb, alpha-cypermethrin, alpha-ecdysone, alpha-endosulfan, amidithion, aminocarb, amiton, amiton oxalate, amitraz, anabasine, athidathion, azadirachtin, azamethiphos, azinphos-ethyl, azinphos-methyl, azothoate, barium hexafluorosilicate, barthrin, bendiocarb, benfuracarb, bensultap, benzpyrimoxan, beta-cyfluthrin, beta-cypermethrin, bifenthrin, bioallethrin, bioethanomethrin, biopermethrin, bistrifluron, borax, boric acid, broflanilide, bromfenvinfos, bromocyclen, bromo-DDT, bromophos, bromophos-ethyl, bufencarb, buprofezin, butacarb, butathiofos, butocarboxim, butonate, butoxycarboxim, cadusafos, calcium arsenate, calcium polysulfide, camphechlor, carbanolate, carbaryl, carbofuran, carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan, cartap, cartap hydrochloride, chlorantraniliprole, chlorbicyclen, chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride, chlorethoxyfos, chlorfenapyr, chlorfenvinphos, chlorfluazuron, chlormephos, chloroform, chloropicrin, chloroprallethrin, chlorphoxim, chlorprazophos, chlorpyrifos, chlorpyrifos-methyl, chlorthiophos, chromafenozide, cinerin I, cinerin II, cinerins, cismethrin, cloethocarb, closantel, clothianidin, copper acetoarsenite, copper arsenate, copper naphthenate, copper oleate, coumaphos, coumithoate, crotamiton, crotoxyphos, crufomate, cryolite, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyclaniliprole, cyclethrin, cycloprothrin, cyfluthrin, cyhalodiamide, cyhalothrin, cypermethrin, cyphenothrin, cyromazine, cythioate, DDT, decarbofuran, deltamethrin, demephion, demephion-O, demephion-S, demeton, demeton-methyl, demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl, demeton-S-methylsulphon, diafenthiuron, dialifos, diatomaceous earth, diazinon, dicapthon, dichlofenthion, dichlorvos, dicloromezotiaz, dicresyl, dicrotophos, dicyclanil, dieldrin, diflubenzuron, dilor, dimefluthrin, dimefox, dimetan, dimethoate, dimethrin, dimethylvinphos, dimetilan, dinex, dinex-diclexine, dinoprop, dinosam, dinotefuran, diofenolan, dioxabenzofos, dioxacarb, dioxathion, disulfoton, dithicrofos, d-limonene, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium, doramectin, ecdysterone, emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothion, endrin, EPN, epofenonane, eprinomectin, epsilon-metofluthrin, epsilon-momfluorothrin, esdepalléthrine, esfenvalerate, etaphos, ethiofencarb, ethion, ethiprole, ethoate-methyl, ethoprophos, ethyl formate, ethyl-DDD, ethylene dibromide, ethylene dichloride, ethylene oxide, etofenprox, etrimfos, EXD, famphur, fenamiphos, fenazaflor, fenchlorphos, fenethacarb, fenfluthrin, fenitrothion, fenobucarb, fenoxacrim, fenoxycarb, fenpirithrin, fenpropathrin, fensulfothion, fenthion, fenthion-ethyl, fenvalerate, fipronil, flometoquin, flonicamid, fluazaindolizine, flubendiamide, flucofuron, flucycloxuron, flucythrinate, fluensulfone, flufenerim, flufenoxuron, flufenprox, flufiprole, fluhexafon, flupyradifurone, flupyrimin, fluvalinate, fluxametamide, fonofos, formetanate, formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosmethilan, fospirate, fosthietan, furathiocarb, furethrin, gamma-cyhalothrin, gamma-HCH, halfenprox, halofenozide, HCH, HEOD, heptachlor, heptafluthrin, heptenophos, heterophos, hexaflumuron, HHDN, hydramethylnon, hydrogen cyanide, hydroprene, hyquincarb, imidacloprid, imiprothrin, indoxacarb, iodomethane, IPSP, isazofos, isobenzan, isocarbophos, isocycloseram, isodrin, isofenphos, isofenphos-methyl, isoprocarb, isoprothiolane, isothioate, isoxathion, ivermectin, jasmolin I, jasmolin II, jodfenphos, juvenile hormone I, juvenile hormone II, juvenile hormone III, kappa-bifenthrin, kappa-tefluthrin, kelevan, kinoprene, lambda-cyhalothrin, lead arsenate, lepimectin, leptophos, lindane, lirimfos, lufenuron, lythidathion, malathion, malonoben, mazidox, mecarbam, mecarphon, menazon, meperfluthrin, mephosfolan, mercurous chloride, mesulfenfos, metaflumizone, methacrifos, methamidophos, methidathion, methiocarb, methocrotophos, methomyl, methoprene, methoxychlor, methoxyfenozide, methyl bromide, methyl isothiocyanate, methylchloroform, methylene chloride, metofluthrin, metolcarb, metoxadiazone, mevinphos, mexacarbate, milbemectin, milbemycin oxime, mipafox, mirex, molosultap, momfluorothrin, monocrotophos, monomehypo, monosultap, morphothion, moxidectin, naftalofos, naled, naphthalene, nicotine, nifluridide, nitenpyram, nithiazine, nitrilacarb, novaluron, noviflumuron, omethoate, oxamyl, oxazosulfyl, oxydemeton-methyl, oxydeprofos, oxydisulfoton, para-dichlorobenzene, parathion, parathion-methyl, penfluron, pentachlorophenol, permethrin, phenkapton, phenothrin, phenthoate, phorate, phosalone, phosfolan, phosmet, phosnichlor, phosphamidon, phosphine, phoxim, phoxim-methyl, pirimetaphos, pirimicarb, pirimiphos-ethyl, pirimiphos-methyl, potassium arsenite, potassium thiocyanate, pp′-DDT, prallethrin, precocene I, precocssene II, precocene III, primidophos, profenofos, profluralin, promacyl, promecarb, propaphos, propetamphos, propoxur, prothidathion, prothiofos, prothoate, protrifenbute, pyflubumide, pyraclofos, pyrafluprole, pyrazophos, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyridaben, pyridalyl, pyridaphenthion, pyrifluquinazon, pyrimidifen, pyriminostrobin, pyrimitate, pyriprole, pyriproxyfen, quassia, quinalphos, quinalphos-methyl, quinothion, rafoxanide, resmethrin, rotenone, ryania, sabadilla, schradan, selamectin, silafluofen, silica gel, sodium arsenite, sodium fluoride, sodium hexafluorosilicate, sodium thiocyanate, sophamide, spinetoram, spinosad, spiromesifen, spiropidion, spirotetramat, sulcofuron, sulcofuron-sodium, sulfluramid, sulfotep, sulfoxaflor, sulfuryl fluoride, sulprofos, tau-fluvalinate, tazimcarb, TDE, tebufenozide, tebufenpyrad, tebupirimfos, teflubenzuron, tefluthrin, temephos, TEPP, terallethrin, terbufos, tetrachlorantraniliprole, tetrachloroethane, tetrachlorvinphos, tetramethrin, tetramethylfluthrin, tetraniliprole, theta-cypermethrin, thiacloprid, thiamethoxam, thicrofos, thiocarboxime, thiocyclam, thiocyclam oxalate, thiodicarb, thiofanox, thiometon, thiosultap, thiosultap-disodium, thiosultap-monosodium, thuringiensin, tioxazafen, tolfenpyrad, tralomethrin, transfluthrin, transpermethrin, triarathene, triazamate, triazophos, trichlorfon, trichlormetaphos-3, trichloronat, trifenofos, triflumezopyrim, triflumuron, trimethacarb, triprene, tyclopyrazoflor, vamidothion, vaniliprole, XMC, xylylcarb, zeta-cypermethrin, zolaprofos, and any combinations thereof.

Additionally, the compounds described herein may be combined with herbicides that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds to form pesticidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the present disclosure may be applied in conjunction with one or more herbicides to control a wide variety of undesirable plants. When used in conjunction with herbicides, the presently claimed compounds may be formulated with the herbicide(s), tank-mixed with the herbicide(s) or applied sequentially with the herbicide(s). Typical herbicides include, but are not limited to: 4-CPA; 4-CPB; 4-CPP; 2,4-D; 3,4-DA; 2,4-DB; 3,4-DB; 2,4-DEB; 2,4-DEP; 3,4-DP; 2,3,6-TBA; 2,4,5-T; 2,4,5-TB; acetochlor, acifluorfen, aclonifen, acrolein, alachlor, allidochlor, alloxydim, allyl alcohol, alorac, ametridione, ametryn, amibuzin, amicarbazone, amidosulfuron, aminocyclopyrachlor, aminopyralid, amiprofos-methyl, amitrole, ammonium sulfamate, anilofos, anisuron, asulam, atraton, atrazine, azafenidin, azimsulfuron, aziprotryne, barban, BCPC, beflubutamid, beflubutamid-M, benazolin, bencarbazone, benfluralin, benfuresate, bensulfuron, bensulide, bentazone, benzadox, benzfendizone, benzipram, benzobicyclon, benzofenap, benzofluor, benzoylprop, benzthiazuron, bicyclopyrone, bifenox, bilanafos, bispyribac, bixlozone, borax, bromacil, bromobonil, bromobutide, bromofenoxim, bromoxynil, brompyrazon, butachlor, butafenacil, butamifos, butenachlor, buthidazole, buthiuron, butralin, butroxydim, buturon, butylate, cacodylic acid, cafenstrole, calcium chlorate, calcium cyanamide, cambendichlor, carbasulam, carbetamide, carboxazole chlorprocarb, carfentrazone, CDEA, CEPC, chlomethoxyfen, chloramben, chloranocryl, chlorazifop, chlorazine, chlorbromuron, chlorbufam, chloreturon, chlorfenac, chlorfenprop, chlorflurazole, chlorflurenol, chloridazon, chlorimuron, chlornitrofen, chloropon, chlorotoluron, chloroxuron, chloroxynil, chlorpropham, chlorsulfuron, chlorthal, chlorthiamid, cinidon-ethyl, cinmethylin, cinosulfuron, cisanilide, clacyfos, clethodim, cliodinate, clodinafop, clofop, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, cloransulam, CMA, copper sulfate, CPMF, CPPC, credazine, cresol, cumyluron, cyanatryn, cyanazine, cycloate, cyclopyranil, cyclopyrimorate, cyclosulfamuron, cycloxydim, cycluron, cyhalofop, cyperquat, cyprazine, cyprazole, cypromid, daimuron, dalapon, dazomet, delachlor, desmedipham, desmetryn, di-allate, dicamba, dichlobenil, dichloralurea, dichlormate, dichlorprop, dichlorprop-P, diclofop, diclosulam, diethamquat, diethatyl, difenopenten, difenoxuron, difenzoquat, diflufenican, diflufenzopyr, dimefuron, dimepiperate, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimexano, dimidazon, dinitramine, dinofenate, dinoprop, dinosam, dinoseb, dinoterb, diphenamid, dipropetryn, diquat, disul, dithiopyr, diuron, DMPA, DNOC, DSMA, EBEP, eglinazine, endothal, epronaz, EPTC, erbon, esprocarb, ethalfluralin, ethametsulfuron, ethidimuron, ethiolate, ethofumesate, ethoxyfen, ethoxysulfuron, etinofen, etnipromid, etobenzanid, EXD, fenasulam, fenoprop, fenoxaprop, fenoxaprop-P, fenoxasulfone, fenquinotrione, fenteracol, fenthiaprop, fentrazamide, fenuron, ferrous sulfate, flamprop, flamprop-M, flazasulfuron, florasulam, florpyrauxifen, fluazifop, fluazifop-P, fluazolate, flucarbazone, flucetosulfuron, fluchloralin, flufenacet, flufenican, flufenpyr, flumetsulam, flumezin, flumiclorac, flumioxazin, flumipropyn, fluometuron, fluorodifen, fluoroglycofen, fluoromidine, fluoronitrofen, fluothiuron, flupoxam, flupropacil, flupropanate, flupyrsulfuron, fluridone, flurochloridone, fluroxypyr, flurtamone, fluthiacet, fomesafen, foramsulfuron, fosamine, furyloxyfen, glufosinate, glufosinate-P, glyphosate, halauxifen, halosafen, halosulfuron, haloxydine, haloxyfop, haloxyfop-P, hexachloroacetone, hexaflurate, hexazinone, imazamethabenz, imazamox, imazapic, imazapyr, imazaquin, imazethapyr, imazosulfuron, indanofan, indaziflam, iodobonil, iodomethane, iodosulfuron, iofensulfuron, ioxynil, ipazine, ipfencarbazone, iprymidam, isocarbamid, isocil, isomethiozin, isonoruron, isopolinate, isopropalin, isoproturon, isouron, isoxaben, isoxachlortole, isoxaflutole, isoxapyrifop, karbutilate, ketospiradox, lancotrione, lactofen, lenacil, linuron, MAA, MAMA, MCPA, MCPA-thioethyl, MCPB, mecoprop, mecoprop-P, medinoterb, mefenacet, mefluidide, mesoprazine, mesosulfuron, mesotrione, metam, metamifop, metamitron, metazachlor, metazosulfuron, metflurazon, methabenzthiazuron, methalpropalin, methazole, methiobencarb, methiozolin, methiuron, methometon, methoprotryne, methyl bromide, methyl isothiocyanate, methyldymron, metobenzuron, metobromuron, metolachlor, metosulam, metoxuron, metribuzin, metsulfuron, molinate, monalide, monisouron, monochloroacetic acid, monolinuron, monuron, morfamquat, MSMA, naproanilide, napropamide, napropamide-M, naptalam, neburon, nicosulfuron, nipyraclofen, nitralin, nitrofen, nitrofluorfen, norflurazon, noruron, OCH, orbencarb, ortho-dichlorobenzene, orthosulfamuron, oryzalin, oxadiargyl, oxadiazon, oxapyrazon, oxasulfuron, oxaziclomefone, oxyfluorfen, parafluron, paraquat, pebulate, pelargonic acid, pendimethalin, penoxsulam, pentachlorophenol, pentanochlor, pentoxazone, perfluidone, pethoxamid, phenisopham, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenylmercury acetate, picloram, picolinafen, pinoxaden, piperophos, potassium arsenite, potassium azide, potassium cyanate, pretilachlor, primisulfuron, procyazine, prodiamine, profluazol, profluralin, profoxydim, proglinazine, prometon, prometryn, propachlor, propanil, propaquizafop, propazine, propham, propisochlor, propoxycarbazone, propyrisulfuron, propyzamide, prosulfalin, prosulfocarb, prosulfuron, proxan, prynachlor, pydanon, pyraclonil, pyraflufen, pyrasulfotole, pyrazolynate, pyrazosulfuron, pyrazoxyfen, pyribenzoxim, pyributicarb, pyriclor, pyridafol, pyridate, pyriftalid, pyriminobac, pyrimisulfan, pyrithiobac, pyroxasulfone, pyroxsulam, quinclorac, quinmerac, quinoclamine, quinonamid, quizalofop, quizalofop-P, rhodethanil, rimsulfuron, saflufenacil, S-metolachlor, sebuthylazine, secbumeton, sethoxydim, siduron, simazine, simeton, simetryn, SMA, sodium arsenite, sodium azide, sodium chlorate, sulcotrione, sulfallate, sulfentrazone, sulfometuron, sulfosulfuron, sulfuric acid, sulglycapin, swep, TCA, tebutam, tebuthiuron, tefuryltrione, tembotrione, tepraloxydim, terbacil, terbucarb, terbuchlor, terbumeton, terbuthylazine, terbutryn, tetrafluron, thenylchlor, thiazafluron, thiazopyr, thidiazimin, thidiazuron, thiencarbazone-methyl, thifensulfuron, thiobencarb, tiafenacil, tiocarbazil, tioclorim, tolpyralate, topramezone, tralkoxydim, triafamone, tri-allate, triasulfuron, triaziflam, tribenuron, tricamba, triclopyr, tridiphane, trietazine, trifloxysulfuron, trifludimoxazin, trifluralin, triflusulfuron, trifop, trifopsime, trihydroxytriazine, trimeturon, tripropindan, tritac, tritosulfuron, vernolate, and xylachlor.

Another embodiment of the present disclosure is a method for the control or prevention of fungal attack. This method comprises applying to the soil, plant, roots, foliage, or locus of the fungus, or to a locus in which the infestation is to be prevented (for example applying to cereal or grape plants), a fungicidally effective amount of one or more of the compounds of Formula I. The compounds are suitable for treatment of various plants at fungicidal levels, while exhibiting low phytotoxicity. The compounds may be useful both in a protectant and/or an eradicant fashion.

The compounds have been found to have significant fungicidal effect particularly for agricultural use. Many of the compounds are particularly effective for use with agricultural crops and horticultural plants.

It will be understood by those skilled in the art that the efficacy of the compound for the foregoing fungi establishes the general utility of the compounds as fungicides.

The compounds have broad ranges of activity against fungal pathogens. Exemplary pathogens may include, but are not limited to, causing agent of wheat leaf blotch (Zymoseptoria tritici), wheat brown rust (Puccinia triticina), wheat stripe rust (Puccinia striiformis), scab of apple (Venturia inaequalis), powdery mildew of grapevine (Uncinula necator), barley scald (Rhynchosporium secalis), blast of rice (Magnaporthe grisea), rust of soybean (Phakopsora pachyrhizi), glume blotch of wheat (Parastagonospora nodorum), powdery mildew of wheat (Blumeria graminis f. sp.tritici), powdery mildew of barley (Blumeria graminis f. sp. hordei), powdery mildew of cucurbits (Erysiphe cichoracearum), anthracnose of cucurbits (Glomerella lagenarium), leaf spot of beet (Cercospora beticola), early blight of tomato (Alternaria solani), and spot blotch of barley (Cochliobolus sativus). The exact amount of the active material to be applied is dependent not only on the specific active material being applied, but also on the particular action desired, the fungal species to be controlled, and the stage of growth thereof, as well as the part of the plant or other product to be contacted with the compound. Thus, all the compounds, and formulations containing the same, may not be equally effective at similar concentrations or against the same fungal species.

The compounds are effective in use with plants in a disease-inhibiting and phytologically acceptable amount. The term “disease-inhibiting and phytologically acceptable amount” refers to an amount of a compound that kills or inhibits the plant disease for which control is desired, but is not significantly toxic to the plant. This amount will generally be from about 0.1 to about 1000 ppm (parts per million), with 1 to 500 ppm being preferred. The exact concentration of compound required varies with the fungal disease to be controlled, the type of formulation employed, the method of application, the particular plant species, climate conditions, and the like. A suitable application rate is typically in the range from about 0.10 to about 4 pounds/acre (about 0.01 to 0.45 grams per square meter, g/m²).

Any range or desired value given herein may be extended or altered without losing the effects sought, as is apparent to the skilled person for an understanding of the teachings herein.

The compounds of Formula I may be made using well-known chemical procedures. Intermediates not specifically mentioned in this disclosure are either commercially available, may be made by routes disclosed in the chemical literature, or may be readily synthesized from commercial starting materials utilizing standard procedures.

General Schemes

The following schemes illustrate approaches to generating picolinamide compounds of Formula (I). The following descriptions and examples are provided for illustrative purposes and should not be construed as limiting in terms of substituents or substitution patterns.

Racemic mixtures of Formulas 1.2-Rac, 1.3-Rac and 1.5-Rac, 1.6-Rac, wherein R₃ is as previously defined, can be prepared by the method shown in Scheme 1, step a. Submission of racemic epoxide mixtures of Formulas 1.0-Rac and 1.4-Rac, to reaction with an organometallic nucleophile, such

as an aryl magnesium halide, in the presence of a metal halide, such as copper iodide, in a polar, aprotic solvent, such as tetrahydrofuran (THF) or diethyl ether (Et₂O), at a temperature of about −78° C. to 55° C., affords racemic mixtures of Formulas 1.2-Rac, 1.3-Rac and 1.5-Rac, 1.6-Rac, wherein R₃ is as previously defined, and shown in step a.

Racemic mixtures of Formulas 1.2-Rac, 1.3-Rac and 1.5-Rac, 1.6-Rac, wherein R₃ is as previously defined, can be separated into their individual enantiomers utilizing a lipase-catalyzed kinetic resolution described by Akita (Tetrahedron: Asymmetry 2009, 20, 1286-1294) and outlined in Scheme 2, steps a and b. Subjection of racemic mixtures of Formulas 1.2-Rac, 1.3-Rac and 1.5-Rac, 1.6-Rac, wherein R₃ is as previously defined, to Candida antarctica lipase B (CAL-B) in an

acetylating solvent, such as vinyl acetate, at a temperature of about 25° C. to about 60° C., affords the unreacted secondary alcohols of Formulas 1.2-Abs and 1.5-Abs, wherein R₃ is as originally defined, and the acetylated compounds of Formulas 2.1-Abs and 2.3-Abs, wherein R₃ is as originally defined. The mixtures can be purified via silica gel chromatography using a hexane-ethyl acetate mixture as the mobile phase giving the resolved secondary alcohols and acetates of Formulas 1.2-Abs, 1.5-Abs, 2.1-Abs and 2.3-Abs, wherein R₃ is as originally defined, and in high enantiomeric excess. The lipase recognition of the secondary alcohol of 1.2-Rac, 1.3-Rac, 1.5-Rac and 1.6-Rac, wherein R₃ is as originally defined, was similar to the empirical rule for the kinetic resolution of secondary alcohols (Bornscheuer and Kazlauskus, Hydrolases in Organic Synthesis; Wiley-VCH, 2006). Treatment of acetates of Formulas 2.1-Abs and 2.3-Abs, wherein R₃ is as originally defined, with a carbonate base, such as potassium carbonate, in an alcoholic solvent, such as methanol, at a temperature of about 25° C. to about 60° C., affords the resolved secondary alcohols of Formulas 2.2-Abs and 2.4-Abs, wherein R₃ is as originally defined.

Compounds of Formula 3.2, wherein R₁, R₂, R₃, and R₁₀, are as originally defined, may be prepared according to the method outlined in Scheme 3, step a. Alcohols of Formula 3.0, wherein R₂ and R₃, are as originally defined, can be treated with compounds of Formula 3.1, wherein R₁ and R₁₀ are as originally defined, a coupling reagent, such as 3-(ethyliminomethyleneamino)-N,N-dimethylpropan-1-amine hydrochloride (EDC) or a polymer-supported carbodiimide (PS-CDI), and a catalyst, such as N,N-dimethylpyridin-4-amine (DMAP), in a halogenated or polar, aprotic solvent, such as (CH₂Cl₂) or THF to afford compounds of Formula 3.2, wherein R₁, R₂, R₃, and R₁₀, are as originally defined, as shown in step a.

Compounds of Formula 4.5, wherein R₁, R₂, R₃, R₅, and R₁₀, are as originally defined, can be prepared according to the methods outlined in Scheme 4, steps a-d. Compounds of Formula 3.2, wherein R₁, R₂, R₃, and R₁₀, are as originally defined, can be treated with an acid, such as a 4 Normal (N) solution of hydrogen chloride (HCl) in dioxane, in a halogenated solvent such as CH₂Cl₂ to afford compounds of Formula 4.1, wherein R₁, R₂, R₃, and R₁₀, as shown in step a. Compounds of Formula 4.2, wherein R₁, R₂, R₃, and R₁₀, are as originally defined, can be prepared by treating compounds of Formula 3.2, wherein R₁, R₂, R₃, and R₁₀, are as originally defined, with an acid, such as 2,2,2-trifluoroacetic acid, in a halogenated solvent such as CH₂Cl₂, as shown in step c. Compounds of Formulas 4.1 and 4.2, wherein R₁, R₂, R₃, and R₁₀, are as originally defined, can be treated with compounds of Formula 4.3, wherein R₅ is as originally defined, in the presence of a base, such as diisopropylethylamine, and a peptide coupling reagent, such as benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) or O-(7-azabenzo-triazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU), in a halogenated solvent such as CH₂Cl₂, to afford compounds of Formula 4.5, wherein R₁, R₂, R₃, R₅ and R₁₀, are as originally defined, as shown in steps b and d.

Compounds of Formula 5.1, wherein R₁, R₂, R₃, R₅ and R₁₀, are as originally defined, can be prepared according to the method outlined in Scheme 5, steps a or b. Compounds of Formula 4.5, wherein R₁, R₂, R₃, R₅ and R₁₀, are as originally defined, can be treated with an appropriate alkyl halide, with or without a reagent such as sodium iodide (NaI) and an alkali carbonate base, such as sodium (Na₂CO₃) or potassium carbonate (K₂CO₃), in a solvent such as acetone, at a temperature of about 25° C. to about 50° C., as shown in step a. Or, alternatively, by treatment with an acyl halide or anhydride in the presence of an amine base, such as pyridine, triethylamine (NEt₃), DMAP, or mixtures thereof, in an aprotic solvent, such as CH₂Cl₂, to afford compounds of Formula 5.1, wherein R₁, R₂, R₃, R₅, R₆, and R₁₀, are as originally defined, as shown in step b.

Compounds of Formula 6.1 and 6.2, wherein R₁, R₂, R₃, R₅, R₆, and R₁₀, are as originally defined, can be prepared according to the method outlined in Scheme 6, steps a and b. Compounds of Formula 4.5, wherein R₁, R₂, R₃, R₅, and R₁₀, are as originally defined, can be treated with a thionating reagent such as phosphorus pentasulfide, an additive, such as hexamethyldisiloxane, optionally in a polar aprotic solvent such as acetonitrile (CH₃CN), at a temperature of about 0° C. to 80° C. to afford compounds of Formula 6.1, wherein R₁, R₂, R₃, R₅ and R₁₀, are as originally defined, and shown in step a. It will be understood by those skilled in the art that compounds such as Formula 6.1 may also be prepared using other thionating agents including, but not limited to: sulfur, sulfhydric acid, sodium sulfide, sodium hydrosulfide, boron trisulfide, bis(diethylaluminum)sulfide, ammonium sulfide, Lawesson's reagent, ammonium O,O′-diethyl dithiophosphate, rhodanine, or a polymer supported thionating reagent. Additives can include, but not limited to, aluminum oxide (Al₂O₃); inorganic bases, such as potassium carbonate and sodium bicarbonate; organic bases, such as triethylamine, diethylaniline, pyridine and morpholine. Optional solvents can include, but not limited to, aliphatic, alicyclic or aromatic hydrocarbons, such as hexane, cyclohexane or toluene; halogenated hydrocarbons, such as dichloromethane, 1,2-dichloroethane and chlorobenzene; ethers, such as diethyl ether, 1,4-dioxane, THF and 1,2-dimethoxyethane; and other polar aprotic solvents such as pyridine and hexamethylphosphoramide (HMPA). In step b, treatment of compounds of Formula 6.1, wherein R₁, R₂, R₃, R₅ and R₁₀, are as originally defined, with an appropriate alkyl halide with or without a reagent such as sodium iodide (NaI) and an alkali carbonate base, such as sodium carbonate (Na₂CO₃) or potassium carbonate (K₂CO₃), in a polar aprotic solvent, such as acetone, at a temperature of about 55° C., or by treatment with an acyl halide or anhydride in the presence of an amine base, such as pyridine, Et₃N, DMAP, or mixtures thereof, in an optional aprotic solvent such as CH₂Cl₂, at a temperature of about 23° C., can afford compounds of Formula 6.2 wherein R₁, R₂, R₃, R₅, R₆, and R₁₀, are as originally defined.

Compounds of Formula 7.1, wherein R₁, R₂, R₃, R₅ and R₁₀, are as originally defined, can be prepared according to the method outlined in Scheme 7, step a. Compounds of Formula 4.5, wherein R₁, R₂, R₃, R₅ and R₁₀, are as originally defined, can be treated with a oxidizing reagent such as m-chloroperbenzoic acid (mCPBA) in a polar solvent such as CH₂Cl₂, at a temperature of about 0° C. to 50° C., to give compounds of Formula 7.1, wherein R₁, R₂, R₃, R₅ and R₁₀, are as previously defined, and shown in a. It will be understood by those skilled in the art that compounds of Formula 7.1, wherein R₁, R₂, R₃, R₅ and R₁₀, are as originally defined, may also be prepared using other oxidizing agents, including, but not limited to: hydrogen peroxide, hydrogen

peroxide-urea complex, magnesium monoperoxyphthalate hexahydrate (MMPP), peroxyacetic acid, oxone, sodium perchlorate or dimethyl dioxirane.

Compounds of Formula 8.1 wherein R₁, R₂, R₃, R₅ and R₁₀, are as originally defined, can be prepared according to the method outlined in Scheme 8, step a. Compounds of Formula 4.5, wherein R₁, R₂, R₃, R₅ and R₁₀, are as originally defined, can be treated with a diactivated carbonyl reagent such as triphosgene, with a base, such as pyridine, and in a polar solvent, such as CH₂Cl₂, at a temperature of about 0° C. to 50° C. to afford compounds of Formula 8.1, wherein R₁, R₂, R₃, R₅ and R₁₀, are as originally defined, as depicted in a.

EXAMPLES Example 1A: Preparation of racemic threo-3-(2,4-dimethylphenyl)butan-2-ol

To a suspension of freshly activated magnesium metal shavings (1.14 g, 46.80 mmol) in anhydrous Et₂O (20 mL) was added dropwise 1-bromo-2,4-dimethylbenzene (8 g, 43.20 mmol). The mixture was gently heated at slight reflux (36° C.) for 5 hours (hr). The resulting dark brown solution was added via syringe to a flask containing copper (I) iodide (4.12 g, 21.61 mmol) suspended in Et₂O (50 mL) at −20° C. The dark yellow suspension was stirred for 15 minutes (min) at −20° C. and then cooled to −50° C. Racemic trans-butene epoxide (1.3 g, 18.01 mmol) was slowly added dropwise followed by warming the reaction to room temperature and stirring overnight. The mixture was then cooled to 0° C. and slowly quenched by the addition of a saturated aqueous ammonium chloride (NH₄Cl) solution. The mixture was filtered through a pad of Celite and the pad was rinsed thoroughly with ethyl acetate. The organic solution was washed with saturated NH₄C₁ solution and brine. The solution was dried (magnesium sulfate (MgSO₄)), filtered and concentrated under reduced pressure. The residue was purified via automated flash column chromatography (SiO₂, 0-40% ethyl acetate/hexanes gradient) to give racemic threo-3-(2,4-dimethylphenyl)butan-2-ol as a yellow oil (813 mg, 25%): ¹H NMR (500 MHz, CDCl₃) δ 7.06 (d, J=8.5 Hz, 1H), 7.01-6.97 (m, 2H), 3.94-3.82 (m, 1H), 2.97 (p, J=6.9 Hz, 1H), 2.29 (d, J=7.7 Hz, 6H), 1.50 (d, J=3.9 Hz, 1H), 1.28 (d, J=7.0 Hz, 3H), 1.11 (d, J=6.3 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) δ 139.99, 135.49, 135.38, 131.31, 126.81, 126.18, 71.92, 41.42, 21.25, 20.87, 19.85, 16.06; EIMS m/z 178.

Example 1B: Preparation of racemic erythro-3-(o-tolyl)butan-2-ol

To a −20° C. suspension of copper(I) iodide (4.15 g, 21.60 mmol) in anhydrous Et₂O (40 mL) was added 2-methylphenylmagnesium bromide (2.0 M in Et₂O, 22.5 mL, 43.20 mmol) slowly dropwise. After stirring for 30 min, the orange suspension was cooled to −78° C., and racemic cis-butene epoxide (1.3 g, 18.01 mmol) was slowly added. The dry ice bath was removed and the mixture was allowed to slowly warm to ambient temperature and stirred overnight. The mixture was cooled with an ice bath to 0° C. and quenched slowly by the dropwise addition of a saturated aqueous NH₄Cl solution. The mixture was warmed to room temperature and filtered through Celite, followed by rinsing the pad with ethyl acetate (EtOAc). The resulting filtrate was washed with saturated aqueous NH₄Cl solution and brine. The solution was then dried (MgSO₄) and concentrated under reduced pressure. The residue was purified automated flash column chromatography (SiO₂, 0-30% ethyl acetate/hexanes gradient) to give racemic erythro-3-(o-tolyl)butan-2-ol (2.05 g, 69%) as a yellow oil: ¹H NMR (500 MHz, CDCl₃) δ 7.34-7.01 (m, 4H), 3.92 (p, J=6.3 Hz, 1H), 3.01 (p, J=7.1 Hz, 1H), 2.36 (s, 3H), 1.47 (s, 1H), 1.28 (d, J=6.1 Hz, 3H), 1.19 (d, J=7.0 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) δ 142.14, 136.84, 130.61, 126.49, 125.81, 72.33, 42.62, 20.47, 19.93, 17.88; EIMS m/z 164.

Example 1C: Preparation of racemic threo-3-phenylbutan-2-ol

To a suspension of copper (I) iodide (1.86 g, 9.76 mmol) in ethyl ether (18.0 mL) was added dropwise phenyllithium (1.9 M in butyl ether, 10.3 mL, 19.53 mmol) at 0° C. under a nitrogen atmosphere. After stirring at 0° C. for 1 hr, racemic trans-2,3-dimethyloxirane (0.64 g, 8.88 mmol) was added dropwise followed by removal of the ice bath and warming to room temperature with stirring over 2 hr. The reaction mixture was quenched with water (20 mL), filtered through a pad of Celite, and extracted with ethyl ether (3×20 mL). The organics were passed through a phase separator and concentrated in vacuo. The crude residue was purified via automated flash column chromatography (SiO₂, 0-25% acetone/hexanes gradient) to furnish racemic threo-3-phenylbutan-2-ol (1.33 g, 8.85 mmol, 99%) as orange oil: ¹H NMR (400 MHz, CDCl₃) δ 7.38-7.12 (m, 5H), 3.91-3.84 (m, 1H), 2.80-2.68 (m, 1H), 1.43 (s, 1H), 1.33 (d, J=7.1 Hz, 3H), 1.09 (d, J=6.3 Hz, 3H). The spectral data was consistent with those reported in the literature: Tetrahedron 1981, 37, 709-713.

Example 2: Preparation of (2S,3S)-3-(2,4-dimethylphenyl)butan-2-ol and (2R,3R)-3-(2,4-dimethylphenyl)butan-2-ol Step 1: Preparation of (2S,3S)-3-(2,4-dimethylphenyl)butan-2-ol and (2R,3R)-3-(2,4-dimethylphenyl)butan-2-yl acetate

A vial containing a solution of the racemic trans-3-(2,4-dimethylphenyl)butan-2-ol (800 mg, 4.49 mmol) dissolved in vinyl acetate (15 mL) was charged with beads of Novozym 435 Lipase (CAL-B, 1.6 g, 4.49 mmol). The vial was placed in an orbital shaker and was shaken at 200 rpm and heated at 55° C. for 7.5 hrs. The reaction was cooled and filtered through a frit disk with an EtOAc rinse. The eluent was concentrated under reduced pressure to give 906 mg of a crude yellow oil. The residue was purified via flash column chromatography (SiO₂, 0-20% ethyl acetate/hexanes gradient) to afford (2R,3R)-3-(2,4-dimethylphenyl)butan-2-yl acetate (clear oil, 466 mg, 47%) followed by (2S,3S)-3-(2,4-dimethylphenyl)butan-2-ol (clear yellow oil, 357 mg, 43%). Acetate: ¹H NMR (500 MHz, CDCl₃) δ 7.07 (d, J=7.7 Hz, 1H), 7.01-6.97 (m, 2H), 5.08 (dq, J=8.5, 6.3 Hz, 1H), 3.16-3.05 (m, 1H), 2.30 (s, 3H), 2.28 (s, 3H), 2.06 (s, 3H), 1.21 (d, J=6.9 Hz, 3H), 1.06 (d, J=6.3 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) δ 170.80, 138.92, 135.56, 135.42, 131.22, 126.93, 126.33, 75.09, 39.48, 21.34, 20.89, 19.88, 18.34, 17.96; EIMS m/z 220. Alcohol: ¹H NMR (500 MHz, CDCl₃) δ 7.06 (d, J=8.5 Hz, 1H), 7.01-6.97 (m, 2H), 3.88 (tt, J=9.2, 4.7 Hz, 1H), 2.97 (p, J=6.9 Hz, 1H), 2.30 (s, 3H), 2.28 (s, 3H), 1.49 (d, J=3.5 Hz, 1H), 1.28 (d, J=7.0 Hz, 3H), 1.11 (d, J=6.3 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) δ 140.00, 135.49, 135.38, 131.31, 126.82, 126.18, 71.92, 41.43, 21.25, 20.87, 19.85, 16.07; EIMS m/z 178. The enatiomeric ratio of (2S,3S)-3-(2,4-dimethylphenyl)butan-2-ol was determined to be 96:4 by analysis via enatiomeric HPLC separation (210 nm wavelength).

Step 2: Preparation of (2R,3R)-3-(2,4-dimethylphenyl)butan-2-ol

To a solution containing (2R,3R)-3-(2,4-dimethylphenyl)butan-2-yl acetate prepared above (458 mg, 2.08 mmol) dissolved in methanol (4.2 mL) was added potassium carbonate (431 mg, 3.12 mmol). The mixture was stirred at ambient temperature for 1.5 hr, then heated to 50° C. for 2 hr. The reaction was cooled and concentrated under reduced pressure. The residue was diluted with acetone and passed through a small plug of silica gel, washing the pad well with acetone. The solvent was concentrated in vacuo to give (2R,3R)-3-(2,4-dimethylphenyl)butan-2-ol (332 mg, 90%) as a yellow oil: ¹H NMR (500 MHz, CDCl₃) δ 7.06 (d, J=8.5 Hz, 1H), 7.01-6.97 (m, 2H), 3.88 (p, J=6.3 Hz, 1H), 2.97 (p, J=6.9 Hz, 1H), 2.30 (s, 3H), 2.28 (s, 3H), 1.49 (s, 1H), 1.28 (d, J=7.0 Hz, 3H), 1.11 (d, J=6.3 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) δ 140.00, 135.49, 135.38, 131.31, 126.82, 126.18, 71.92, 41.43, 21.26, 20.87, 19.85, 16.07; EIMS m/z 178. The enatiomeric ratio of the alcohol was determined to be 7:93 via analysis by enatiomeric HPLC.

Example 3: Preparation of (2S,3S)-3-phenylbutan-2-ol (tert-butoxycarbonyl)-L-alaninate

To a solution of (2S,3S)-3-phenylbutan-2-ol (0.23 g, 1.53 mmol) dissolved in methylene chloride (7.7 mL) was added N-ethyl-N-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.59 g, 3.06 mmol) and N,N-dimethylpyridin-4-amine (19 mg, 0.15 mmol). The reaction mixture was purged with nitrogen, stirred over 16 hr, followed by concentration in vacuo. The crude residue was purified via automated flash column chromatography (SiO₂, 0-20% ethyl acetate/hexanes gradient) to afford (2S,3S)-3-phenylbutan-2-yl (tert-butoxycarbonyl)-L-alaninate (0.43 g, 1.34 mmol, 83% yield) as colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 7.35-7.25 (m, 2H), 7.27-7.15 (m, 3H), 5.12-5.01 (m, 2H), 4.35-4.26 (m, 1H), 2.95-2.83 (m, 1H), 1.45 (s, 9H), 1.37 (d, J=7.2 Hz, 3H), 1.29 (d, J=7.1 Hz, 3H), 1.09 (d, J=6.3 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) δ 172.9, 155.0, 143.0, 128.5, 127.8, 126.7, 79.7, 76.1, 49.5, 45.1, 28.3, 18.9, 18.3, 17.5; IR (thin film) 3355, 2978, 2934, 1711, 1495, 1452, 1366, 1161, 1087, 1065, 701 cm⁻¹.

Example 4: Preparation of (2S,3S)-3-phenylbutan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate Step 1: Preparation of (2S,3S)-3-phenylbutan-2-yl-L-alaninate·hydrochloride

To neat (2S,3S)-3-phenylbutan-2-ol (tert-butoxycarbonyl)-L-alaninate (0.42 g, 1.31 mmol) was added dropwise a solution of HCl dissolved in dioxane (4 M, 3.3 mL, 13.07 mmol) under nitrogen. Upon stirring for 16 hr, the reaction mixture was concentrated in vacuo to afford crude (2S,3S)-3-phenylbutan-2-yl-L-alaninate·hydrogen chloride as white solid, which was directly carried to the next step: HRMS-ESI (m/z) [M+H]+ calc'd for C₁₃H₂₀NO₂, 222.1489; found, 222.1485.

Step 2: Preparation of (2S,3S)-3-phenylbutan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate

To a solution of (2S,3S)-3-phenylbutan-2-yl-L-alaninate·hydrogen chloride, 3-hydroxy-4-methoxypicolinic acid (0.24 g, 1.44 mmol), and (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (0.75 g, 1.44 mmol) dissolved in methylene chloride (6.5 mL) was added dropwise N,N-diisopropylethylamine (0.75 mL, 4.31 mmol) under nitrogen. Upon stirring for 16 hr, the reaction mixture was concentrated in vacuo. The crude residue was purified via automated flash column chromatography (SiO₂, 0-45% acetone/hexanes gradient) to afford (2S,3S)-3-phenylbutan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (0.46 g, 1.173 mmol, 90% yield) as colorless oil: ¹H NMR (500 MHz, CDCl₃) δ 12.16 (s, 1H), 8.50 (d, J=8.0 Hz, 1H), 8.01 (d, J=5.2 Hz, 1H), 7.32-7.27 (m, 2H), 7.24-7.16 (m, 3H), 6.88 (d, J=5.2 Hz, 1H), 5.11 (dq, J=7.7, 6.3 Hz, 1H), 4.77-4.67 (m, 1H), 3.95 (s, 3H), 2.97-2.87 (m, 1H), 1.54 (d, J=7.2 Hz, 3H), 1.31 (d, J=7.0 Hz, 3H), 1.13 (d, J=6.3 Hz, 3H); IR (thin film) 2978, 2937, 1733, 1647, 1527, 1451, 1262, 1147, 701 cm⁻¹; HRMS-ESI (m/z) [M+H]+ calc'd for C₂₀H₂₅N₂O₅, 373.1758; found, 373.1752.

Example 5A: Preparation of (2S,3S)-3-phenylbutan-2-yl (3-acetoxy-4-methoxypicolinoyl)-L-alaninate

To a solution containing (2S,3S)-3-phenylbutan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (84 mg, 0.23 mmol) dissolved in pyridine (1.0 mL) was added dropwise acetic anhydride (0.25 mL, 2.65 mmol) under nitrogen. Upon stirring for 30 min, the reaction mixture was concentrated in vacuo, followed by azeotroping with toluene (10 mL). The crude residue was purified via automated flash column chromatography (SiO₂, 0-40% acetone/hexanes gradient) to afford (2S,3S)-3-phenylbutan-2-yl (3-acetoxy-4-methoxypicolinoyl)-L-alaninate (90 mg, 0.21 mmol, 91% yield) as colorless oil: ¹H NMR (500 MHz, CDCl₃) δ 8.56 (s, 1H), 8.34 (d, J=5.5 Hz, 1H), 7.32-7.27 (m, 2H), 7.24-7.16 (m, 3H), 7.01 (d, J=5.5 Hz, 1H), 5.09 (dq, J=7.7, 6.3 Hz, 1H), 4.77-4.67 (m, 1H), 3.91 (s, 3H), 2.96-2.86 (m, 1H), 2.41 (s, 3H), 1.49 (d, J=7.2 Hz, 3H), 1.30 (d, J=7.0 Hz, 3H), 1.10 (d, J=6.3 Hz, 3H); IR (thin film) 3377, 2980, 2938, 1770, 1732, 1674, 1507, 1310, 1198, 1174, 702 cm⁻¹; HRMS-ESI (m/z) [M+H]+ calc'd for C₂₂H₂₇N₂O₆, 415.1864; found, 415.1859.

Example 5B: Preparation of (2S,3R)-3-(o-tolyl)butan-2-yl (3-(acetoxymethoxy)-4-methoxypicolinoyl)-L-alaninate

To a solution containing (2S,3R)-3-(o-tolyl)butan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate dissolved in 0.7 mL of acetone was added potassium carbonate (39 mg, 0.279 mmol) followed by bromomethyl acetate (27 μL, 0.279 mmol). The solution was heated at 50° C. for 1.5 hr. The reaction mixture was cooled and concentrated in vacuo. The crude residue was purified via automated flash column chromatography (SiO₂, 0-80% acetone/hexanes gradient) to afford (2S,3R)-3-(o-tolyl)butan-2-yl (3-(acetoxymethoxy)-4-methoxypicolinoyl)-L-alaninate (63 mg, 93% yield) as a thick oil: ¹H NMR (500 MHz, CDCl₃) δ 8.26 (d, J=5.4 Hz, 1H), 8.22 (t, J=7.4 Hz, 1H), 7.22-7.03 (m, 4H), 6.93 (d, J=5.4 Hz, 1H), 5.73 (dd, J=5.6, 1.8 Hz, 2H), 5.16 (dq, J=8.1, 6.3 Hz, 1H), 4.58-4.51 (m, 1H), 3.90 (s, 3H), 3.31-3.22 (m, 1H), 2.37 (s, 3H), 2.06 (s, 3H), 1.31 (d, J=6.2 Hz, 3H), 1.24 (d, J=7.0 Hz, 3H), 1.03 (d, J=7.2 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) δ 172.26, 170.26, 162.87, 160.25, 145.68, 143.94, 142.57, 141.57, 136.03, 130.21, 126.16, 125.94, 109.49, 89.57, 75.57, 56.16, 48.08, 39.48, 20.87, 19.84, 17.92, 17.77, 17.05; HRMS-ESI (m/z) [M+H]⁺ calc'd for C₂₄H₃₀N₂O₇, 459.2126; found, 459.2121.

Example 5C: Preparation of 4-methoxy-2-(((S)-1-oxo-1-(((2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl)oxy)propan-2-yl)carbamoyl)pyridin-3-yl isobutyrate

To a solution containing (2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (283.9 mg, 0.645 mmol) and N,N-dimethylpyridin-4-amine (15.75 mg, 0.129 mmol) was prepared in CH₂Cl₂ (2 mL). To this solution was added triethylamine (0.180 mL, 1.289 mmol) followed by isobutyryl chloride (0.102 mL, 0.967 mmol). The resultant clear reaction was stirred at ambient temperature overnight. The reaction was concentrated under reduced pressure to afford an orange oil under a stream of N₂. The crude residue was purified via automated flash column chromatography (SiO₂, 0-100% ethyl acetate/hexanes gradient) to afford 4-methoxy-2-(((S)-1-oxo-1-(((2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl)oxy)propan-2-yl)carbamoyl)pyridin-3-yl isobutyrate (252.3 mg, 0.494 mmol, 77% yield) as a yellow oil: ¹H NMR (400 MHz, CDCl₃) δ 8.50 (d, J=7.4 Hz, 1H), 8.34 (d, J=5.4 Hz, 1H), 7.64 (dd, J=8.0, 1.3 Hz, 1H), 7.54-7.47 (m, 1H), 7.44 (d, J=7.8 Hz, 1H), 7.31 (t, J=7.5 Hz, 1H), 6.99 (d, J=5.4 Hz, 1H), 5.26-5.11 (m, 1H), 4.76 (p, J=7.3 Hz, 1H), 3.89 (s, 3H), 3.34 (p, J=6.6 Hz, 1H), 2.96 (hept, J=7.0 Hz, 1H), 1.54 (d, J=7.2 Hz, 3H), 1.36 (dd, J=7.0, 1.3 Hz, 6H), 1.28 (d, J=6.8 Hz, 3H), 1.10 (d, J=6.3 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −58.25; IR (thin film) 3383, 2981, 1737, 1679, 1505, 1310, 1114, 1045, 732 cm⁻¹; HRMS-ESI (m/z) [M+H]⁺ calc'd for C₂₅H₃₀F₃N₂O₆, 511.2050; found, 511.2048.

Example 6: Preparation of (2S,3S)-3-(2,4-dimethylphenyl)butan-2-yl (3-acetoxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate Step 1: Preparation of (2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl (3-hydroxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate

To a solution containing (2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (120.1 mg, 0.273 mmol) dissolved in acetonitrile (2.73 mL) was added phosphorus pentasulfide (121 mg, 0.545 mmol) followed by 1,1,1,3,3,3-hexamethyldisiloxane (291 μL, 1.363 mmol) added in one portion. The reaction was heated to 45° C. for 30 min. The reaction was cooled, diluted with CH₂Cl₂ (10 mL) and quenched by the addition of saturated aqueous NaHCO₃ (10 mL). The layers were separated and the aqueous layer was extracted with CH₂Cl₂ (3×10 mL). The combined organic layers were passed through a phase separator and concentrated to a yellow oil. The crude material was purified via automated flash column chromatography (SiO₂, 0-50% acetone/hexanes gradient) to afford (2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl (3-hydroxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate (104.7 mg, 0.229 mmol, 84% yield) as a yellow semisolid; ¹H NMR (400 MHz, CDCl₃) δ 12.93 (s, 1H), 10.74 (d, J=7.6 Hz, 1H), 8.00 (d, J=5.1 Hz, 1H), 7.73-7.59 (m, 1H), 7.51 (t, J=7.7 Hz, 1H), 7.43 (d, J=7.8 Hz, 1H), 7.33 (t, J=7.5 Hz, 1H), 6.89 (d, J=5.1 Hz, 1H), 5.30-5.18 (m, 1H), 5.14 (p, J=7.2 Hz, 1H), 3.96 (s, 3H), 3.37 (p, J=6.8 Hz, 1H), 1.69 (dd, J=7.2, 3.2 Hz, 3H), 1.30 (d, J=6.8 Hz, 3H), 1.14 (d, J=6.3 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −58.23; IR (thin film) 3087, 2984, 1737, 1513, 1484, 1311, 1151, 1118, 800, 771 cm⁻¹; HRMS-ESI (m/z) [M+H]⁺ calc'd for C₂₁H₂₄F₃N₂O₄S, 457.1403; found, 457.1399.

Step 2: Preparation of (2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl (3-acetoxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate

To a solution containing (2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl (3-hydroxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate (53.9 mg, 0.118 mmol) and N,N-dimethylpyridin-4-amine (2.89 mg, 0.024 mmol) dissolved in CH₂Cl₂ (2 mL) was added triethylamine (0.041 mL, 0.295 mmol) followed by acetyl chloride (9.23 μL, 0.130 mmol). The resultant light orange reaction was stirred at ambient temperature for 18 hr. The reaction was concentrated under reduced pressure to afford an orange oil under a stream of N₂. The crude residue was purified via automated flash column chromatography (SiO₂, 0-50% acetone/hexanes gradient) to afford (2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl (3-acetoxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate (51.7 mg, 0.104 mmol, 88% yield) as a yellow oil: ¹H NMR (400 MHz, CDCl₃) δ 9.96 (d, J=7.3 Hz, 1H), 8.34 (d, J=5.5 Hz, 1H), 7.71-7.59 (m, 1H), 7.59-7.47 (m, 1H), 7.44 (d, J=7.8 Hz, 1H), 7.39-7.28 (m, 1H), 7.00 (d, J=5.5 Hz, 1H), 5.28-5.15 (m, 2H), 3.91 (s, 3H), 3.42-3.29 (m, 1H), 2.37 (s, 3H), 1.64 (d, J=7.2 Hz, 3H), 1.30 (d, J=6.8 Hz, 3H), 1.12 (d, J=6.3 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −58.23; HRMS-ESI (m/z) [M+H]⁺ calc'd for C₂₃H₂₆F₃N₂O₅S, 499.1509; found, 499.1508.

Example 7: Preparation of 3-hydroxy-4-methoxy-2-(((S)-1-oxo-1-(((2S,3S)-3-phenylbutan-2-yl)oxy)propan-2-yl)carbamoyl)pyridine 1-oxide

To a solution containing (2S,3S)-3-phenylbutan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (54 mg, 0.15 mmol) dissolved in methylene chloride (1.0 mL) was added m-CPBA (50 mg, 0.29 mmol). Upon stirring for 30 min at room temperature, the reaction mixture was concentrated in vacuo. The crude residue was purified via automated flash column chromatography (SiO₂, 0-50% acetone/hexanes gradient) to afford 3-hydroxy-4-methoxy-2-(((S)-1-oxo-1-(((2S,3S)-3-phenylbutan-2-yl)oxy)propan-2-yl)carbamoyl)pyridine 1-oxide (51 mg, 0.13 mmol, 86% yield) as viscous, pale yellow oil: ¹H NMR (500 MHz, CDCl₃) δ 14.39 (s, 1H), 12.82 (d, J=6.9 Hz, 1H), 7.89 (d, J=7.2 Hz, 1H), 7.32-7.25 (m, 2H), 7.25-7.15 (m, 3H), 6.78 (d, J=7.2 Hz, 1H), 5.10 (dq, J=8.1, 6.3 Hz, 1H), 4.75-4.64 (m, 1H), 3.97 (s, 3H), 2.96-2.86 (m, 1H), 1.56 (d, J=7.2 Hz, 3H), 1.30 (d, J=6.9 Hz, 3H), 1.12 (d, J=6.2 Hz, 3H); IR (thin film) 2978, 2937, 1735, 1643, 1569, 1479, 1452, 1211, 1154, 729, 702 cm⁻¹; HRMS-ESI (m/z) [M+H]+ calc'd for C₂₀H₂₅N₂O₆, 389.1707; found, 389.1703.

Example 8: Preparation of (2S,3S)-3-phenylbutan-2-yl (S)-2-(8-methoxy-2,4-dioxo-2H-pyrido[2,3-e][1,3]oxazin-3 (4H)-yl)propanoate

To a solution containing (2S,3S)-3-phenylbutan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (54 mg, 0.15 mmol) and triphosgene (86 mg, 0.29 mmol) dissolved in methylene chloride (1.0 mL) was added pyridine (0.1 mL, 1.24 mmol). Upon stirring for 45 min, the reaction mixture was quenched with saturated sodium bicarbonate solution (5 mL) and extracted with methylene chloride (3×5 mL). The organics were passed through a phase separator and concentrated in vacuo. The crude residue was purified via automated flash column chromatography (SiO₂, 0-40% acetone/hexanes gradient) to afford (2S,3S)-3-phenylbutan-2-yl (S)-2-(8-methoxy-2,4-dioxo-2H-pyrido[2,3-e][1,3]oxazin-3(4H)-yl)propanoate (41 mg, 0.10 mmol, 67% yield) as an off-white foam: ¹H NMR (500 MHz, CDCl₃) δ 8.61 (d, J=5.3 Hz, 1H), 7.24-7.17 (m, 2H), 7.17-7.06 (m, 4H), 5.61 (q, J=7.1 Hz, 1H), 5.16-5.06 (m, 1H), 4.06 (s, 3H), 2.93-2.83 (m, 1H), 1.70 (d, J=7.1 Hz, 3H), 1.27 (d, J=7.1 Hz, 3H), 1.04 (d, J=6.3 Hz, 3H); IR (thin film) 2978, 2942, 1769, 1712, 1602, 1501, 1371, 1242, 1081, 702 cm¹; HRMS-ESI (m/z) [M+H]+ calc'd for C₂₁H₂₃N₂O₆, 399.1551; found, 399.1549.

Example A: Evaluation of Fungicidal Activity: Leaf Blotch of Wheat (Zymoseptoria tritici; Bayer Code SEPTTR)

Technical grades of materials were dissolved in acetone, which were then mixed with nine volumes of water containing 110 ppm Triton X-100. The fungicide solutions were applied onto wheat seedlings using an automated booth sprayer to run-off. All sprayed plants were allowed to air dry prior to further handling. All fungicides were evaluated using the aforementioned method for their activity vs. all target diseases, unless stated otherwise. Wheat leaf blotch and brown rust activity were also evaluated using track spray applications, in which case the fungicides were formulated as EC formulations, containing 0.1% Trycol 5941 in the spray solutions.

Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Zymoseptoria tritici either prior to or after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two to three days in a lighted dew chamber at 20° C.) to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 20° C. for disease to develop. When disease symptoms were fully expressed on the 1^(st) leaves of untreated plants, infection levels were assessed on a scale of 0 to 100 percent disease severity. Percent disease control was calculated using the ratio of disease severity on treated plants relative to untreated plants.

Example B: Evaluation of Fungicidal Activity: Wheat Brown Rust (Puccinia triticina; Synonym: Puccinia recondita f. Sp. Tritici; Bayer Code PUCCRT)

Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Puccinia triticina either prior to or after fungicide treatments. After inoculation the plants were kept in a dark dew room at 22° C. with 100% relative humidity overnight to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 24° C. for disease to develop. Fungicide formulation, application and disease assessment followed the procedures as described in the Example A.

Example C: Evaluation of Fungicidal Activity: Asian Soybean Rust (Phakopsora pachyrhizi; Bayer Code PHAKPA)

Technical grades of materials were dissolved in acetone, which were then mixed with nine volumes of water containing 0.011% Tween 20. The fungicide solutions were applied onto soybean seedlings using an automated booth sprayer to run-off. All sprayed plants were allowed to air dry prior to further handling.

Soybean plants (variety Williams 82) were grown in soil-less Metro mix, with one plant per pot. Two week old seedlings were used for testing. Plants were inoculated either 3 days prior to or 1 day after fungicide treatments. Plants were incubated for 24 h in a dark dew room at 22° C. and 100% relative humidity then transferred to a growth room at 23° C. for disease to develop. Disease severity was assessed on the sprayed leaves.

Example D: Evaluation of Fungicidal Activity: Tomato Early Blight (Alternaria solani; Bayer Code ALTESO)

Tomato plants (variety Outdoor Girl) were propagated in soil-less Metro mix, with each pot having one plant, and used when 12 to 14 days old. Test plants were inoculated with an aqueous spore suspension of Alternaria solani 24 hr after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two to three days in a lighted dew chamber at 20° C.) to permit spores to germinate and infect the leaf. The plants were then transferred to a growth room at 22° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.

Example E: Evaluation of Fungicidal Activity: Leaf Spot of Sugar Beets (Cercospora beticola; Bayer Code CERCBE)

Sugar beet plants (variety HH88) were grown in soil-less Metro mix and trimmed regularly to maintain a uniform plant size prior to test. Plants were inoculated with a spore suspension 24 hr after fungicide treatments. Inoculated plants were kept in a dew chamber at 22° C. for 48 hr then incubated in a greenhouse set at 24° C. under a clear plastic hood with bottom ventilation until disease symptoms were fully expressed. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.

Example F: Evaluation of Fungicidal Activity: Cucumber Anthracnose (Glomerella lagenarium; Anamorph: Colletotrichum lagenarium; Bayer Code COLLLA)

Cucumber seedlings (variety Bush Pickle) were propagated in soil-less Metro mix, with each pot having one plant, and used in the test when 12 to 14 days old. Test plants were inoculated with an aqueous spore suspension of Colletotrichum lagenarium 24 hr after fungicide treatments. After inoculation the plants were kept in a dew room at 22° C. with 100% relative humidity for 48 hr to permit spores to germinate and infect the leaf. The plants were then transferred to a growth room set at 22° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.

Example G: Evaluation of Fungicidal Activity: Wheat Glume Blotch (Parastagonospora nodorum; Bayer Code LEPTNO)

Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Parastagonospora nodorum 24 hr after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two days in a lighted dew chamber at 20° C.) to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 20° C. for disease to develop. Fungicide formulation, application and disease assessment followed the procedures as described in the Example A.

Example H: Evaluation of Fungicidal Activity: Cucumber Downy Mildew (Pseudoperonospora cubensis; Bayer Code PSPECU)

Cucumber seedlings (variety Bush Pickle) were grown in soil-less Metro mix, with one plant per pot, and used in the test when 12 to 14 days old. Plants were inoculated with a spore suspension 24 hr following fungicide treatments. Test plants were inoculated with an aqueous spore suspension of Pseudoperonospora cubensis 24 hr after fungicide treatments. After inoculation the plants were kept in a dew room at 22° C. with 100% relative humidity for 24 hr to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 20° C. until disease was fully expressed. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.

Example I: Evaluation of Fungicidal Activity: Rice Blast (Magnaporthe grisea; Anamorph: Pyricularia oryzae; Bayer Code PYRIOR)

Rice seedlings (variety Japonica) were propagated in soil-less Metro mix, with each pot having 8 to 14 plants, and used in the test when 12 to 14 days old. Test plants were inoculated with an aqueous spore suspension of Pyricularia oryzae 24 hr after fungicide treatments. After inoculation, the plants were kept in a dew room at 22° C. with 100% relative humidity for 48 hr to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 24° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.

Example J: Evaluation of Fungicidal Activity: Barley Scald (Rhyncosporium secalis, Bayer Code RHYNSE)

Barley seedlings (variety Harrington) were propagated in soil-less Metro mix, with each pot having 8 to 12 plants, and used in the test when first leaf was fully emerged. Test plants were inoculated by an aqueous spore suspension of Rhyncosporium secalis 24 hr after fungicide treatments. After inoculation the plants were kept in a dew room at 20° C. with 100% relative humidity for 48 hr. The plants were then transferred to a greenhouse set at 20° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.

Example K: Evaluation of Fungicidal Activity: Grape Powdery Mildew (Uncinula necator; Bayer Code UNCINE)

Grape seedlings (variety Carignane) were grown in soil-less Metro mix, with one plant per pot, and used in the test when approximately 1 month old. Plants were inoculated 24 hr after fungicide treatment by shaking spores from infected leaves over test plants. Plants were maintained in a greenhouse set at 20° C. until disease was fully developed. Fungicide formulation, application and disease assessment on sprayed leaves followed the procedures as described in the Example A.

TABLE 1 Compound Structure, Appearance, and Preparation Method As Prepared Cmpd. According No. Structure To Appearance 1

Example 1A Example 2 Example 3 Oil 2

Example 1A Example 2 Example 3 Oil 3

Example 1A Example 2 Example 3 Oil 4

Example 1A Example 2 Example 3 Oil 5

Example 1A Example 2 Example 3 Oil 6

Example 1A Example 2 Example 3 Oil 7

Example 1A Example 2 Example 3 Oil 8

Example 1A Example 2 Example 3 Oil 9

Example 1B Example 2 Example 3 Oil 10

Example 1B Example 2 Example 3 Oil 11

Example 1B Example 2 Example 3 Oil 12

Example 1B Example 2 Example 3 Oil 13

Example 1B Example 2 Example 3 Oil 14

Example 1B Example 2 Example 3 Oil 15

Example 1B Example 2 Example 3 Oil 16

Example 1B Example 2 Example 3 Oil 17

Example 1B Example 2 Example 3 Oil 18

Example 1B Example 2 Example 3 Oil 19

Example 1B Example 2 Example 3 Oil 20

Example 1B Example 2 Example 3 Oil 21

Example 1A Example 2 Example 3 Oil 22

Example 1B Example 2 Example 3 Oil 23

Example 1A Example 2 Example 3 Oil 24

Example 1A Example 2 Example 3 Oil 25

Example 1A Example 2 Example 3 Oil 26

Example 1A Example 2 Example 3 Oil 27

Example 1A Example 2 Example 3 Oil 28

Example 1A Example 2 Example 3 Oil 29

Example 1B Example 2 Example 3 Oil 30

Example 1B Example 2 Example 3 Oil 31

Example 1B Example 2 Example 3 Oil 32

Example 1B Example 2 Example 3 Oil 33

Example 1B Example 2 Example 3 Oil 34

Example 1B Example 2 Example 3 Oil 35

Example 1B Example 2 Example 3 Oil 36

Example 1B Example 2 Example 3 Oil 37

Example 1B Example 2 Example 3 Oil 38

Example 1B Example 2 Example 3 Oil 39

Example 1B Example 2 Example 3 Oil 40

Example 1B Example 2 Example 3 Oil 41

Example 1A Example 2 Example 3 Light Yellow Oil 42

Example 1A Example 2 Example 3 Clear Oil 43

Example 1A Example 2 Example 3 Reddish Brown Oil 44

Example 1A Example 2 Example 3 Orange Oil 45

Example 1A Example 2 Example 3 Yellow Oil 46

Example 1A Example 2 Example 3 Yellow Oil 47

Example 1 Example 3 Clear, Colorless Oil 48

Example 1A Example 3 Pale Yellow Oil 49

Example 1 Example 2 Example 3 Clear, Colorless Oil 50

Example 1A Example 2 Example 3 Pale Yellow Oil 51

Example 1A Example 2 Example 3 Clear, Colorless Oil 52

Example 1A Example 2 Example 3 Clear, Colorless Oil 53

Example 1B Example 2 Example 3 Colorless Oil 54

Example 1C Example 2 Example 3 Colorless Oil 55

Example 1B Example 2 Example 3 Yellow Oil 56

Example 1B Example 2 Example 3 Colorless Oil 57

Example 1B Example 2 Example 3 Residue 58

Example 4 Step 1 Oil 59

Example 4 Step 1 Oil 60

Example 4 Step 1 Oil 61

Example 4 Step 1 Oil 62

Eample 4 Step 1 Oil 63

Example 4 Step 1 Oil 64

Example 4 Step 1 Oil 65

Example 4 Step 1 Oil 66

Example 4 Step 1 Oil 67

Example 4 Step 1 Oil 68

Example 4 Step 1 Oil 69

Example 4 Step 1 Oil 70

Example 4 Step 1 Oil 71

Example 4 Step 1 Oil 72

Example 4 Step 1 Oil 73

Example 4 Step 1 Oil 74

Example 4 Step 1 Oil 75

Example 4 Step 1 Oil 76

Example 4 Step 1 Oil 77

Example 4 Step 1 Oil 78

Example 4 Step 1 Oil 79

Example 4 Step 1 Oil 80

Example 4 Step 1 Oil 81

Example 4 Step 1 Oil 82

Example 4 Step 1 Oil 83

Example 4 Step 1 Oil 84

Example 4 Step 1 Oil 85

Example 4 Step 1 Oil 86

Example 4 Step 1 Oil 87

Example 4 Step 1 Oil 88

Example 4 Step 1 Oil 89

Example 4 Step 1 Oil 90

Example 4 Step 1 Oil 91

Example 4 Step 1 Oil 92

Example 4 Step 1 Oil 93

Example 4 Step 1 Oil 94

Example 4 Step 1 Oil 95

Example 4 Step 1 Oil 96

Example 4 Step 1 Oil 97

Example 4 Step 1 Oil 98

Example 4 Step 1 Dark Yellow Oil 99

Example 4 Step 1 Dark Yellow Oil 100

Example 4 Step 1 Brown Semisolid 101

Example 4 Step 1 Light Brown Semisolid 102

Example 1A Example 2 Example 3 Example 4 Step 1 Pale Yellow Oil 103

Example 4 Step 1 Orange Semisolid 104

Example 4 Step 1 Orange Semisolid 105

Example 1A Example 2 Example 3 Example 4 Step 1 White Semisolid 106

Example 4 Step 1 White Semisolid 107

Example 4 Step 1 Pale Yellow Oil 108

Example 4 Step 1 White Semisolid 109

Example 4 Step 1 Clear, Colorless Glass 110

Example 4 Step 1 Clear, Colorless Oil 111

Example 4 Step 1 Clear, Colorless Oil 112

Example 4 Step 1 Colorless Oil 113

Example 4 Step 1 White Solid 114

Example 4 Step 1 Yellow Oil 115

Example 4 Step 1 Colorless Oil 116

Example 4 Step 2 Thick Clear Oil 117

Example 4 Step 2 Thick Clear Oil 118

Example 4 Step 2 White Solid 119

Example 4 Step 2 White Solid 120

Example 4 Step 2 Thick Oil 121

Example 4 Step 2 Thick Oil 122

Example 4 Step 2 Thick Oil 123

Example 4 Step 2 White SOlid 124

Example 4 Step 2 Thick Oil 125

Example 4 Step 2 Thick Oil 126

Example 4 Step 2 White Solid 127

Example 4 Step 2 Thick Oil 128

Example 4 Step 2 White Solid 129

Example 4 Step 2 Thick Oil 130

Example 4 Step 2 White Solid 131

Example 4 Step 2 Thick Oil 132

Example 4 Step 2 Thick Oil 133

Example 4 Step 2 Thick Oil 134

Example 4 Step 2 Thick Oil 135

Example 4 Step 2 Thick Oil 136

Example 4 Step 2 Thick Oil 137

Example 4 Step 2 Thick Oil 138

Example 4 Step 2 White Solid 139

Example 4 Step 2 Thick Oil 140

Example 4 Step 2 Thick Oil 141

Example 4 Step 2 White Solid 142

Example 4 Step 2 Thick Oil 143

Example 4 Step 2 Thick Oil 144

Example 4 Step 2 Thick Oil 145

Example 4 Step 2 Think Oil 146

Example 4 Step 2 Thick Oil 147

Example 4 Step 2 Thick Oil 148

Example 4 Step 2 Thick Oil 149

Example 4 Step 2 Thick Oil 150

Example 4 Step 2 Thick Oil 151

Example 4 Step 2 Thick Oil 152

Example 4 Step 2 Thick Oil 153

Example 4 Step 2 White Solid 154

Example 4 Step 2 Thick Oil 155

Example 4 Step 2 White Solid 156

Example 4 Step 2 Thick Oil 157

Example 4 Step 2 Thick Oil 158

Example 4 Step 2 Orange Oil 159

Example 4 Step 2 Orange Oil 160

Example 4 Step 2 Pale Yellow Oil 161

Example 4 Step 2 Yellow Oil 162

Example 4 Step 2 Yellow Oil 163

Example 4 Step 2 Clear, Colorless Oil 164

Example 4 Step 2 Yellow Oil 165

Example 4 Step 2 Orange Oil 166

Example 4 Step 2 Clear, Colorless Oil 167

Example 4 Step 2 Yellow Oil 168

Example 4 Step 2 Clear, Colorless Oil 169

Example 4 Step 2 Yellow Oil 170

Example 4 Step 2 Colorless Oil 171

Example 4 Step 2 Colorless Oil 172

Example 4 Step 2 Pale Yellow Oil 173

Example 4 Step 2 Colorless Oil 174

Example 4 Step 2 Clear Oil 175

Eample 4 Step 2 Colorless Foam 176

Example 4 Step 2 Residue 177

Example 5A Thick Oil 178

Example 5A Thick Oil 179

Example 5C Thick Oil 180

Example 5C Thick Oil 181

Example 5A Thick Oil 182

Eample 5A Thick Oil 183

Example 5A Thick Oil 184

Example 5A Thick Oil 185

Example 5A Thick Oil 186

Example 5A Thick Oil 187

Example 5A Thick Oil 188

Example 5A Thick Oil 189

Example 5A Thick Oil 190

Eaxmple 5A Thick Oil 191

Example 5A Thick Oil 192

Example 5A Thick Oil 193

Example 5A Thick Oil 194

Example 5A Thick Oil 195

Example 5A Thick Oil 196

Example 5C Thick Oil 197

Example 5C Thick Oil 198

Example 5C Thick Oil 199

Example 5C Thick Oil 200

Example 5C Thick Oil 201

Example 5C Thick Oil 202

Example 5C Thick Oil 203

Example 5C Thick Oil 204

Example 5C Thick Oil 205

Example 5C Thick Oil 206

Example 5C Thick Oil 207

Example 5C Thick Oil 208

Example 5C Thick Oil 209

Example 5C Thick Oil 210

Example 5C Thick Oil 211

Example 5C Thick Oil 212

Example 5C Thick Oil 213

Example 5C Thick Oil 214

Example 5C Thick Oil 215

Example 5C Thick Oil 216

Example 5C Thick Oil 217

Example 5C Thick Oil 218

Example 5C Thick Oil 219

Example 5C Thick Oil 220

Example 5A Thick Oil 221

Example 5C Thick Oil 222

Example 5C Thick Oil 223

Example 5C Thick Oil 224

Example 5C Thick OIl 225

Example 5C Thick Oil 226

Example 5C Thick Oil 227

Example 5C Thick Oil 228

Example 5C Thick Oil 229

Example 5C Thick Oil 230

Example 5C Thick Oil 231

Example 5B Thick Oil 232

Example 5B Thick Oil 233

Example 5B Thick Oil 234

Example 5C Yellow Oil 235

Example 5C Pale Yellow Oil 236

Example 5C Yellow Oil 237

Example 5C Clear, Colorless Oil 238

Example 5C Clear, Colorless Oil 239

Example 5C Clear, Colorless Oil 240

Example 5C Clear, Colorless Oil 241

Example 5C Clear, Colorless Oil 242

Example 5C Clear, Colorless Oil 243

Example 5C Clear, Colorless Oil 244

Example 5C Clear, Colorless Oil 245

Example 5C Yellow Oil 246

Example 5C Pale Yellow Oil 247

Example 5C Clear, Colorless Oil 248

Example 5C Clear, Colorless Oil 249

Example 5C Clear, Colorless Oil 250

Example 5C Clear, Colorless Oil 251

Example 5C Clear, Colorless Oil 252

Example 5C Clear, Colorless Oil 253

Example 5C Clear, Colorless Oil 254

Example 5C Clear, Colorless Oil 255

Example 5C Clear, Colorless Oil 256

Example 5C Clear, Colorless Oil 257

Example 5A Colorless Oil 258

Eaxmple 5A Colorless Oil 259

Example 5A Pale Yellow Oil 260

Example 5A Colorless Oil 261

Example 8 Off-White Foam 262

Example 8 Tan Foam 263

Example 5A Clear Oil 264

Example 5A Clear Oil 265

Example 5C Clear Oil 266

Example 5C Colorless Oil 267

Example 6 Step 1 Yellow Semisolid 268

Example 6 Step 1 Yellow Semisolid 269

Example 6 Step 1 Orange Semisolid 270

Example 6 Step 2 Yellow Oil 271

Example 6 Step 2 Yellow Oil 272

Example 6 Step 2 Yellow Oil 273

Example 7 Yellow Oil 274

Example 7 Pale Yellow Oil 275

Example 7 Pale Yellow Oil 276

Example 7 Pale Yellow Oil 277

Example 7 Pale Yellow Oil 278

Example 5C White Solid 279

Example 5C White Solid 280

Example 5C Yellow Oil 281

Example 5C Clear Oil 282

Example 5C White Solid 284

Example 5C Thick Yellow Oil 285

Example 5C Glassy Solid *Cmpd. No. - Compound Number

TABLE 2 Analytical Data Melting Cmpd. Point IR No. (° C.) (cm⁻¹) MASS SPEC NMR 1 ESIMS m/z 362.3 ([M + Na]⁺) 2 ESIMS m/z 354.3 ([M + H]⁺) 3 ESIMS m/z 382.3 ([M + H]⁺) 4 ESIMS m/z 376.3 ([M + Na]⁺) 5 ESIMS m/z 362.3 ([M + Na]⁺) 6 ESIMS m/z 354.3 ([M + H]⁺) 7 ESIMS m/z 382.3 ([M + H]⁺) 8 ESIMS m/z 354.3 ([M + H]⁺) 9 ESIMS m/z 344.3 ([M + Na]⁺) 10 ESIMS m/z 336.5 ([M + H]⁺) 11 ESIMS m/z 364.3 ([M + H]⁺) 12 ESIMS m/z 336.2 ([M + H]⁺) 13 ESIMS m/z 348.2 ([M + Na]⁺) 14 ESIMS m/z 340.5 ([M + H]⁺) 15 ESIMS m/z 390.3 ([M + Na]⁺) 16 ESIMS m/z 340.2 ([M + H]⁺) 17 ESIMS m/z 374.3 ([M + Na]⁺) 18 ESIMS m/z 366.3 ([M + H]⁺) 19 ESIMS m/z 394.3 ([M + H]⁺) 20 ESIMS m/z 366.3 ([M + H]⁺) 21 ESIMS m/z 362.3 ([M + Na]⁺) 22 ESIMS m/z 376.3 ([M + Na]⁺) 23 ESIMS m/z 382.3 ([M + H]⁺) 24 ESIMS m/z 354.3 ([M + H]⁺) 25 ESIMS m/z 362.3 ([M + Na]⁺) 26 ESIMS m/z 376.3 ([M + Na]⁺) 27 ESIMS m/z 382.3 ([M + H]⁺) 28 ESIMS m/z 376.3 ([M + Na]⁺) 29 ESIMS m/z 344.3 ([M + Na]⁺) 30 ESIMS m/z 336.2 ([M + H]⁺) 31 ESIMS m/z 364.3 ([M + H]⁺) 32 ESIMS m/z 336.3 ([M + H]⁺) 33 ESIMS m/z 348.2 ([M + Na]⁺) 34 ESIMS m/z 340.3 ([M + H]⁺) 35 ESIMS m/z 368.3 ([M + H]⁺) 36 ESIMS m/z 340.3 ([M + H]⁺) 37 ESIMS m/z 374.3 ([M + Na]⁺) 38 ESIMS m/z 366.3 ([M + H]⁺) 39 ESIMS m/z 394.4 ([M + H]⁺) 40 ESIMS m/z 366.3 ([M + H]⁺) 41 ESIMS m/z 372.3 ([M + Na]⁺) 42 ESIMS m/z 372.3 ([M + Na]⁺) 43 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 7.64 film) 3355, [M + Na]⁺ calcd for (dd, J = 7.8, 1.4 Hz, 1H), 7.52 (td, J = 2981, 1711, C₁₉H₂₆F₃NNaO₄, 7.6, 1.3 Hz, 1H), 7.43 (d, J = 7.9 Hz, 1310, 1150, 412.1706; found, 1H), 7.35-7.28 (m, 1H), 5.25-5.13 1116, 1046, 412.1698 (m, 1H), 5.08 (d, J = 7.9 Hz, 1H), 4.42- 770 cm⁻¹ 4.28 (m, 1H), 3.41-3.27 (m, 1H), 1.46 (s, 9H), 1.43 (d, J = 7.2 Hz, 3H), 1.27 (d, J = 6.8 Hz, 3H), 1.07 (d, J = 6.3 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −58.25. 44 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 7.42 film) 3362, [M + Na]⁺ calcd for (dd, J = 8.8, 5.4 Hz, 1H), 7.35 (dd, J = 2982, 1711, C₁₉H₂₅F₄NNaO₄, 9.2, 2.8 Hz, 1H), 7.23 (td, J = 8.2, 2.8 1499, 1314, 430.1612; found, Hz, 1H), 5.18-5.09 (m, 1H), 5.07 (d, 1154, 1121, 430.1607 J = 7.6 Hz, 1H), 4.41-4.27 (m, 1H), 1046, 909, 3.36-3.24 (m, 1H), 1.46 (s, 9H), 1.42 879 cm⁻¹ (d, J = 7.3 Hz, 3H), 1.26 (d, J = 6.8 Hz, 3H), 1.08 (d, J = 6.2 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −58.81, −114.05. 45 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 7.64 film) 3364, [M + Na]⁺ calcd for (dd, J = 8.0, 1.3 Hz, 1H), 7.52 (td, J = 2981, 1712, C₁₉H₂₆F₃NNaO₄, 7.6, 1.3 Hz, 1H), 7.43 (d, J = 7.8 Hz, 1310, 1150, 412.1706; found, 1H), 7.32 (t, J = 7.6 Hz, 1H), 5.25- 1116, 1046, 412.1699 5.13 (m, 1H), 5.04 (d, J = 7.8 Hz, 1H), 770 cm⁻¹ 4.42-4.26 (m, 1H), 3.40-3.26 (m, 1H), 1.46 (s, 9H), 1.41 (d, J = 7.3 Hz, 3H), 1.29 (d, J = 6.7 Hz, 3H), 1.05 (d, J = 6.2 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −58.25. 46 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 7.42 film) 2981, [M + Na]⁺ calcd for (dd, J = 8.8, 5.3 Hz, 1H), 7.35 (dd, J = 1711, 1498, C₁₉H₂₅F₄NNaO₄, 9.2, 2.8 Hz, 1H), 7.23 (td, J = 8.3, 2.9 1314, 1154, 430.1612; found, Hz, 1H), 5.20-5.09 (m, 1H), 5.02 (d, 1120, 1045, 430.1603 J = 7.8 Hz, 1H), 4.42-4.23 (m, 1H), 909, 879, 3.29 (tt, J = 7.6, 6.0 Hz, 1H), 1.46 (s, 739 cm⁻¹ 9H), 1.40 (d, J = 7.2 Hz, 3H), 1.28 (d, J = 6.8 Hz, 3H), 1.07 (d, J = 6.4 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −58.78, −58.80, −114.19. 47 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 7.05- film) 3357, [M + NH₄]⁺ calcd 6.91 (m, 3H), 5.58 (ddq, J = 10.5, 8.3, 2977, 1713, for C₂₀H₃₅N₂O₄, 6.2 Hz, 1H), 5.11 (s, 1H), 4.42-4.28 1500, 1452, 367.2587; found, (m, 1H), 3.49-3.33 (m, 1H), 2.44- 1365, 1162, 367.2587 2.33 (m, 6H), 1.46 (d, J = 1.1 Hz, 9H), 1055, 1006, 1.45-1.39 (m, 3H), 1.27 (dd, J = 7.1, 769 cm⁻¹ 3.5 Hz, 3H), 1.02 (dd, J = 7.7, 6.2 Hz, 3H). 48 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 6.70 film) 3357, [M + Na]⁺ calcd for (ddd, J = 16.1, 9.4, 2.9 Hz, 2H), 5.53 2978, 1712, C₂₀H₃₀FNNaO₄, (ddq, J = 10.5, 8.6, 6.2 Hz, 1H), 5.11 1366, 1162, 390.2051; found, (s, 1H), 4.41-4.26 (m, 1H), 3.44- 1057, 1023, 390.2048 3.27 (m, 1H), 2.40 (d, J = 1.7 Hz, 3H), 1006, 857 2.35 (s, 3H), 1.46 (s, 9H), 1.45-1.38 cm⁻¹ (m, 3H), 1.25 (dd, J = 7.2, 3.8 Hz, 3H), 1.01 (dd, J = 7.6, 6.2 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −118.37, −118.44. 49 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 7.04- film) 3361, [M + Na]⁺ calcd for 6.93 (m, 3H), 5.58 (ddq, J = 10.4, 8.3, 2977, 1713, C₂₀H₃₁NNaO₄, 6.2 Hz, 1H), 5.10 (d, J = 7.3 Hz, 1H), 1365, 1162, 372.2145; found, 4.43-4.27 (m, 1H), 3.48-3.29 (m, 1056, 1006, 372.2144 1H), 2.41 (d, J = 1.6 Hz, 3H), 2.37 (s, 769 cm⁻¹ 3H), 1.46 (d, J = 1.1 Hz, 9H), 1.45- 1.39 (m, 3H), 1.27 (dd, J = 7.1, 3.5 Hz, 3H), 1.02 (dd, J = 7.7, 6.2 Hz, 3H). 50 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 6.70 film) 3359, [M + Na]⁺ calcd for (ddd, J = 16.2, 9.4, 2.9 Hz, 2H), 5.53 2978, 1712, C₂₀H₃₀FNNaO₄, (ddq, J = 10.5, 8.6, 6.2 Hz, 1H), 5.09 1450, 1366, 390.2051; found, (s, 1H), 4.43-4.28 (m, 1H), 3.34 (dp, 1163, 1057, 390.2050 J = 10.3, 6.9 Hz, 1H), 2.40 (d, J = 1.7 1023, 1006, Hz, 3H), 2.35 (s, 3H), 1.46 (s, 9H), 858, 732 1.45-1.36 (m, 3H), 1.26 (d, J = 3.8 cm⁻¹ Hz, 3H), 1.01 (dd, J = 7.6, 6.2 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −118.40, −118.46. 51 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 7.03- film) 3356, [M + Na]⁺ calcd for 6.94 (m, 3H), 5.58 (ddq, J = 10.5, 8.3, 2977, 1713, C₂₀H₃₁NNaO₄, 6.2 Hz, 1H), 5.10 (d, J = 7.1 Hz, 1H), 1500, 1452, 372.2145; found, 4.43-4.27 (m, 1H), 3.50-3.34 (m, 1163, 1056, 372.2137 1H), 2.41 (d, J = 1.6 Hz, 3H), 2.37 (s, 769 cm⁻¹ 3H), 1.46 (d, J = 1.1 Hz, 9H), 1.45- 1.36 (m, 3H), 1.27 (dd, J = 7.2, 3.5 Hz, 3H), 1.02 (dd, J = 7.7, 6.2 Hz, 3H). 52 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 6.70 film) 3358, [M + Na]⁺ calcd for (ddd, J = 16.0, 9.4, 2.9 Hz, 2H), 5.53 2978, 1712, C₂₀H₃₀FNNaO₄, (ddq, J = 10.5, 8.5, 6.2 Hz, 1H), 5.11 1366, 1163, 390.2051; found, (s, 1H), 4.33 (q, J = 7.3 Hz, 1H), 3.35 1058, 1023, 390.2051 (ddq, J = 13.0, 10.4, 7.1, 6.5 Hz, 1H), 1006, 858, 2.40 (d, J = 1.8 Hz, 3H), 2.35 (s, 3H), 733 cm⁻¹ 1.46 (s, 9H), 1.45-1.39 (m, 3H), 1.25 (dd, J = 7.2, 3.8 Hz, 3H), 1.01 (dd, J = 7.6, 6.2 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −118.39, −118.45. 53 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 7.23- film) 3357, [M + Na]⁺ calcd for 7.12 (m, 2H), 6.96-6.79 (m, 2H), 5.24 2977, 2936, C₁₉H₂₉NO₅Na, (dq, J = 7.7, 6.3 Hz, 1H), 5.00 (d, J = 2837, 1711, 374.1938; found, 6.6 Hz, 1H), 4.19-4.10 (m, 1H), 3.81 1493, 1241, 374.1944 (s, 3H), 3.43 (p, J = 7.3 Hz, 1H), 1.42 1161, 1052, (s, 9H), 1.25-1.20 (m, 6H), 0.99 (d, J = 752 cm⁻¹ 7.1 Hz, 3H). 54 IR (thin ¹H NMR (400 MHz, CDCl₃) δ 7.35- film) 3355, 7.25 (m, 2H), 7.27-7.15 (m, 3H), 2978, 2934, 5.12-5.01 (m, 2H), 4.35-4.26 (m, 1H), 1711, 1495, 2.95-2.83 (m, 1H), 1.45 (s, 9H), 1.37 1452, 1366, (d, J = 7.2 Hz, 3H), 1.29 (d, J = 7.1 Hz, 1161, 1087, 3H), 1.09 (d, J = 6.3 Hz, 3H). 1065, 701 ¹³C NMR (126 MHz, CDCl₃) δ 172.9, cm⁻¹ 155.0, 143.0, 128.5, 127.8, 126.7, 79.7, 76.1, 49.5, 45.1, 28.3, 18.9, 18.3, 17.5. 55 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 6.64- film) 3365, [M + Na]⁺ calcd for 6.53 (m, 2H), 5.11-5.05 (m, 1H), 5.06- 2977, 2933, C₁₇H₂₇NO₄SNa, 4.95 (m, 1H), 4.35-4.26 (m, 1H), 1712, 1500, 364.1553; found, 3.20-3.08 (m, 1H), 2.43 (d, J = 1.2 1449, 1365, 364.1551 Hz, 3H), 1.45 (s, 9H), 1.38 (d, J = 7.2 1161, 1065, Hz, 3H), 1.31 (d, J = 7.1 Hz, 3H), 1.16 796 cm⁻¹ (d, J = 6.3 Hz, 3H). 56 IR (thin HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 7.08 film) 3365, [M + Na]⁺ calcd for (dd, J = 8.5, 6.7 Hz, 1H), 6.65-6.53 2978, 2937, C₁₉H₂₈FNO₅Na, (m, 2H), 5.16-5.07 (m, 1H), 5.05 (d, J = 1708, 1601, 392.1844; found, 7.6 Hz, 1H), 4.30-4.23 (m, 1H), 1502, 1163, 392.1839 3.80 (s, 3H), 3.38-3.29 (m, 1H), 1.45 1035, 952, (s, 9H), 1.35 (d, J = 7.2 Hz, 3H), 1.23 834 cm⁻¹ (d, J = 7.1 Hz, 3H), 1.10 (d, J = 6.3 Hz, 3H). 57 ¹H NMR (300 MHz, CDCl₃) δ 7.13- 6.95 (m, 2H), 6.77-6.52 (m, 2H), 5.11 (d, J = 7.8 Hz, 1H), 5.00 (dq, J = 8.2, 6.2 Hz, 1H), 4.31 (t, J = 7.4 Hz, 1H), 2.92 (s, 6H), 1.45 (s, 9H), 1.39 (d, J = 7.2 Hz, 3H), 1.31-1.17 (m, 4H), 1.08 (d, J = 6.3 Hz, 3H). ¹³C NMR (75 MHz, CDCl₃) δ 172.95, 171.16, 155.04, 149.48, 130.86, 128.41, 112.69, 60.40, 49.51, 44.14, 40.70, 28.35, 18.93, 18.27, 17.82, 14.21. 58 ESIMS m/z 240.2 ([M + H]⁺) 59 ESIMS m/z 240.2 ([M + H]⁺) 60 ESIMS m/z 222.2 ([M + H]⁺) 61 ESIMS m/z 248.9 ([M + Na]⁺) 62 ESIMS m/z 252.2 ([M + H]⁺) 63 ESIMS m/z 240.2 ([M + H]⁺) 64 ESIMS m/z 240.2 ([M + H]⁺) 65 ESIMS m/z 222.2 ([M + H]⁺) 66 ESIMS m/z 226.2 ([M + H]⁺) 67 ESIMS m/z 252.2 ([M + H]⁺) 68 ESIMS m/z 254.2 ([M + H]⁺) 69 ESIMS m/z 254.2 ([M + H]⁺) 70 ESIMS m/z 236.2 ([M + H]⁺) 71 ESIMS m/z 240.2 ([M + H]⁺) 72 ESIMS m/z 266.3 ([M + H]⁺) 73 ESIMS m/z 254.2 ([M + H]⁺) 74 ESIMS m/z 254.2 ([M + H]⁺) 75 ESIMS m/z 236.2 ([M + H]⁺) 76 ESIMS m/z 240.2 ([M + H]⁺) 77 ESIMS m/z 266.3 ([M + H]⁺) 78 ESIMS m/z 282.3 ([M + H]⁺) 79 ESIMS m/z 282.2 ([M + H]⁺) 80 ESIMS m/z 264.3 ([M + H]⁺) 81 ESIMS m/z 268.2 ([M + H]⁺) 82 ESIMS m/z 294.3 ([M + H]⁺) 83 ESIMS m/z 282.2 ([M + H]⁺) 84 ESIMS m/z 282.2 ([M + H]⁺) 85 ESIMS m/z 264.3 ([M + H]⁺) 86 ESIMS m/z 268.2 ([M + H]⁺) 87 ESIMS m/z 294.3 ([M + H]⁺) 88 ESIMS m/z 254.2 ([M + H]⁺) 89 ESIMS m/z 254.2 ([M + H]⁺) 90 ESIMS m/z 236.2 ([M + H]⁺) 91 ESIMS m/z 240.2 ([M + H]⁺) 92 ESIMS m/z 266.3 ([M + H]⁺) 93 ESIMS m/z 254.2 ([M + H]⁺) 94 ESIMS m/z 254.2 ([M + H]⁺) 95 ESIMS m/z 236.2 ([M + H]⁺) 96 ESIMS m/z 240.2 ([M + H]⁺) 97 ESIMS m/z 266.3 ([M + H]⁺) 98 ESIMS m/z 250.3 ([M + H]⁺) 99 ESIMS m/z 250.3 ([M + H]⁺) 100 ESIMS m/z 290.2 ([M + H]⁺) 101 ESIMS m/z 308.1 ([M + H]⁺) 102 ESIMS m/z 214.2 ([M + H]⁺) 103 ESIMS m/z 290.2 ([M + H]⁺) 104 ESIMS m/z 308.1 ([M + H]⁺) 105 ESIMS m/z 214.2 ([M + H]⁺) 106 ESIMS m/z 250.2 ([M + H]⁺) 107 ESIMS m/z 268.2 ([M + H]⁺) 108 ESIMS m/z 250.2 ([M + H]⁺) 109 ESIMS m/z 268.2 ([M + H]⁺) 110 ESIMS m/z 250.2 ([M + H]⁺) 111 ESIMS m/z 268.2 ([M + H]⁺) 112 HRMS-ESI (m/z) [M + H]⁺ calcd for C₁₄H₂₂NO₃, 252.1600; found, 252.1443 113 HRMS-ESI (m/z) [M + H]⁺ calcd for C₁₃H₂₀NO₂, 222.1489; found, 222.1485 114 IR (thin film) 2854, 1740, 1233, 1203, 1118, 1078, 872, 796 cm⁻¹ 115 HRMS-ESI (m/z) [M + H]⁺ calcd for C₁₄H₂₁FNO₃, 270.1500; found, 270.1501 116 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.16 [M + H]⁺ calcd for (s, 1H), 8.52 (d, J = 7.8 Hz, 1H), 8.00 C₂₂H₂₉N₂O₅, (d, J = 5.2 Hz, 1H), 7.09-7.03 (m, 401.2071; found, 1H), 7.00-6.94 (m, 2H), 6.88 (d, J = 401.2067 5.1 Hz, 1H), 5.13 (dq, J = 8.4, 6.2 Hz, 1H), 4.79-4.67 (m, 1H), 3.95 (s, 3H), 3.16 (dq, J = 8.9, 7.0 Hz, 1H), 2.31 (s, 3H), 2.28 (s, 3H), 1.57 (d, J = 7.2 Hz, 3H), 1.24 (d, J = 6.9 Hz, 3H), 1.14 (d, J = 6.2 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.86, 168.68, 155.38, 148.77, 140.50, 138.63, 135.76, 135.33, 131.31, 130.52, 126.97, 126.26, 109.44, 56.08, 48.18, 39.45, 20.89, 19.87, 18.48, 18.46, 17.56. 117 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.17 [M + H]⁺ calcd for (d, J = 0.6 Hz, 1H), 8.50 (d, J = 7.9 Hz, C₂₂H₂₉N₂O₅, 1H), 8.01 (d, J = 5.2 Hz, 1H), 7.10- 401.2071; found, 7.02 (m, 1H), 6.97 (d, J = 6.9 Hz, 2H), 401.2064 6.88 (d, J = 5.2 Hz, 1H), 5.16 (dq, J = 8.4, 6.2 Hz, 1H), 4.77-4.68 (m, 1H), 3.95 (s, 3H), 3.19-3.09 (m, 1H), 2.31 (s, 3H), 2.27 (s, 3H), 1.54 (d, J = 7.2 Hz, 3H), 1.23 (d, J = 6.9 Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.87, 168.72, 155.38, 148.76, 140.50, 138.60, 135.72, 135.36, 131.29, 130.53, 127.00, 126.28, 109.44, 56.08, 47.99, 39.42, 20.87, 19.88, 18.31, 18.26, 17.65. 118 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.04 [M + H]⁺ calcd for (s, 1H), 8.46 (t, J = 5.8 Hz, 1H), 8.01 C₂₀H₂₃FN₂O₅, (d, J = 5.2 Hz, 1H), 7.18-7.06 (m, 391.1664; found, 1H), 6.93-6.79 (m, 3H), 5.15 (dq, J = 391.1662 8.0, 6.3 Hz, 1H), 4.21 (dd, J = 5.7, 3.2 Hz, 2H), 3.95 (s, 3H), 3.15 (p, J = 7.1 Hz, 1H), 2.33 (s, 3H), 1.24 (d, J = 6.9 Hz, 3H), 1.15 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 169.32, 168.74, 161.97, 160.03, 155.39, 148.70, 140.61, 137.91, 137.20, 130.40, 127.85, 117.11, 116.95, 113.07, 112.90, 109.54, 76.40, 56.10, 41.03, 39.10, 20.00, 18.22, 17.42. 119 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.01 [M + H]⁺ calcd for (s, 1H), 8.34 (t, J = 5.8 Hz, 1H), 7.99 C₂₀H₂₃FN₂O₅, (d, J = 5.2 Hz, 1H), 7.15 (dd, J = 9.5, 391.1664; found, 5.8 Hz, 1H), 6.88 (d, J = 5.2 Hz, 1H), 391.1660 6.85-6.75 (m, 2H), 5.24-5.10 (m, 1H), 4.23-3.92 (m, 5H), 3.23 (p, J = 7.1 Hz, 1H), 2.33 (s, 3H), 1.25 (m, 6H). ¹³C NMR (126 MHz, CDCl₃) δ 169.19, 168.38, 161.97, 160.02, 155.38, 148.68, 140.55, 138.37, 136.63, 130.36, 127.68, 116.81, 116.65, 112.86, 112.70, 109.52, 75.82, 56.09, 40.88, 38.65, 19.86, 17.20, 16.64. 120 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.03 [M + H]⁺ calcd for (s, 1H), 8.34 (t, J = 5.8 Hz, 1H), 7.99 C₂₀H₂₄N₂O₅, (d, J = 5.2 Hz, 1H), 7.20 (dd, J = 7.6, 373.1758; found, 1.3 Hz, 1H), 7.16-7.06 (m, 3H), 6.87 373.1754 (d, J = 5.2 Hz, 1H), 5.24-5.17 (m, 1H), 4.16-3.89 (m, 2H), 3.95 (s, 3H), 3.29 (p, J = 7.1 Hz, 1H), 2.35 (s, 3H), 1.27 (m, 6H). ¹³C NMR (126 MHz, CDCl₃) δ 169.15, 168.40, 155.35, 148.66, 140.97, 140.52, 136.10, 130.41, 130.27, 126.30, 126.20, 126.14, 109.48, 75.92, 56.08, 40.85, 39.18, 19.79, 17.18, 16.37. 121 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.04 [M + H]⁺ calcd for (s, 1H), 8.46 (t, J = 5.8 Hz, 1H), 8.01 C₁₉H₂₁FN₂O₅, (d, J = 5.2 Hz, 1H), 7.15 (dd, J = 8.6, 377.1507; found, 5.5 Hz, 2H), 7.01-6.94 (m, 2H), 6.89 377.1504 (d, J = 5.2 Hz, 1H), 5.16-5.05 (m, 1H), 4.21 (dd, J = 5.8, 2.1 Hz, 2H), 3.95 (s, 3H), 2.92 (p, J = 7.1 Hz, 1H), 1.28 (d, J = 7.0 Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 169.33, 168.65, 162.66, 160.72, 155.40, 148.71, 140.61, 138.35, 130.40, 129.27, 129.21, 115.36, 115.19, 109.55, 76.35, 56.10, 44.12, 41.06, 17.83, 17.27. 122 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.06 [M + H]⁺ calcd for (s, 1H), 8.47 (t, J = 5.8 Hz, 1H), 8.01 C₂₁H₂₆N₂O₆, (d, J = 5.2 Hz, 1H), 7.08 (d, J = 8.4 Hz, 403.1864; found, 1H), 6.88 (d, J = 5.2 Hz, 1H), 6.77- 403.1835 6.66 (m, 2H), 5.15 (dq, J = 8.2, 6.3 Hz, 1H), 4.22 (dd, J = 5.7, 2.0 Hz, 2H), 3.95 (s, 3H), 3.77 (s, 3H), 3.18-3.07 (m, 1H), 2.32 (s, 3H), 1.23 (d, J = 6.9 Hz, 3H), 1.14 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 169.30, 168.80, 157.71, 155.38, 148.69, 140.60, 136.96, 133.70, 130.44, 127.36, 115.97, 111.49, 109.52, 76.84, 56.09, 55.12, 41.05, 39.03, 20.17, 18.27, 17.59. 123 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.04 [M + H]⁺ calcd for (s, 1H), 8.46 (t, J = 5.8 Hz, 1H), 8.00 C₂₀H₂₃FN₂O₅, (d, J = 5.2 Hz, 1H), 7.20-7.08 (m, 391.1664; found, 1H), 6.93-6.80 (m, 3H), 5.15 (dq, J = 391.1662 7.9, 6.3 Hz, 1H), 4.21 (dd, J = 5.7, 3.2 Hz, 2H), 3.95 (s, 3H), 3.15 (p, J = 7.1 Hz, 1H), 2.33 (s, 3H), 1.24 (d, J = 6.9 Hz, 3H), 1.15 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 169.32, 168.75, 161.97, 160.03, 155.39, 148.70, 140.61, 137.91, 137.85, 137.20, 137.17, 130.40, 127.85, 127.78, 117.11, 116.95, 113.06, 112.90, 109.54, 76.40, 56.10, 41.03, 39.10, 19.99, 18.22, 17.42. 124 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.01 [M + H]⁺ calcd for (d, J = 0.6 Hz, 1H), 8.34 (t, J = 5.8 Hz, C₂₀H₂₃FN₂O₅, 1H), 7.99 (d, J = 5.2 Hz, 1H), 7.15 (dd, 391.1664; found, J = 9.5, 5.8 Hz, 1H), 6.88 (d, J = 5.2 391.1661 Hz, 1H), 6.85-6.77 (m, 2H), 5.21- 5.11 (m, 1H), 4.20-3.91 (m, 2H), 3.95 (s, 3H), 3.23 (p, J = 7.1 Hz, 1H), 2.33 (s, 3H), 1.30-1.20 (m, 6H). ¹³C NMR (126 MHz, CDCl₃) δ 169.19, 168.38, 161.97, 160.02, 155.38, 148.68, 140.55, 138.43, 136.66, 130.36, 127.75, 127.68, 116.81, 116.65, 112.86, 112.70, 109.52, 75.82, 56.09, 40.88, 38.65, 19.85, 17.20, 16.64. 125 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.03 [M + H]⁺ calcd for (d, J = 0.6 Hz, 1H), 8.34 (t, J = 5.8 Hz, C₂₀H₂₄N₂O₅, 1H), 7.99 (d, J = 5.2 Hz, 1H), 7.20 (dd, 373.1758; found, J = 7.7, 1.3 Hz, 1H), 7.17-7.04 (m, 373.1755 3H), 6.87 (d, J = 5.2 Hz, 1H), 5.25- 5.16 (m, 1H), 4.12 (dd, J = 18.2, 5.9 Hz, 1H), 3.95 (s, 3H), 3.98-3.89 (m, 1H), 3.29 (p, J = 7.1 Hz, 1H), 2.35 (s, 3H), 1.27 (m, 6H). ¹³C NMR (126 MHz, CDCl₃) δ 169.15, 168.41, 155.35, 148.66, 140.97, 140.52, 136.10, 130.41, 130.27, 126.30, 126.14, 109.48, 75.92, 56.08, 40.85, 39.18, 19.79, 17.18, 16.37. 126 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.04 [M + H]⁺ calcd for (s, 1H), 8.46 (t, J = 5.9 Hz, 1H), 8.01 C₁₉H₂₁FN₂O₅, (d, J = 5.2 Hz, 1H), 7.22-7.08 (m, 377.1507; found, 2H), 6.98 (t, J = 8.7 Hz, 2H), 6.89 (d, 377.1507 J = 5.2 Hz, 1H), 5.16-5.01 (m, 1H), 4.29-4.14 (m, 2H), 3.95 (s, 3H), 2.92 (p, J = 7.1 Hz, 1H), 1.28 (d, J = 7.0 Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 169.33, 168.65, 162.67, 160.72, 155.41, 148.71, 140.61, 138.37, 130.40, 129.27, 129.21, 115.36, 115.19, 109.55, 76.36, 56.10, 44.12, 41.06, 17.83, 17.27. 127 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.06 [M + H]⁺ calcd for (s, 1H), 8.47 (t, J = 5.7 Hz, 1H), 8.01 C₂₁H₂₆N₂O₆, (d, J = 5.2 Hz, 1H), 7.08 (d, J = 8.4 Hz, 403.1864; found, 1H), 6.88 (d, J = 5.2 Hz, 1H), 6.82- 403.1853 6.66 (m, 2H), 5.15 (dq, J = 8.1, 6.3 Hz, 1H), 4.29-4.15 (m, 2H), 3.95 (s, 3H), 3.77 (s, 3H), 3.17-3.08 (m, 1H), 2.32 (s, 3H), 1.23 (d, J = 6.9 Hz, 3H), 1.14 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 169.30, 168.80, 157.71, 155.38, 148.69, 140.60, 136.96, 133.70, 130.44, 127.36, 115.97, 111.49, 109.52, 76.84, 56.09, 55.12, 41.05, 39.03, 20.17, 18.27, 17.59. 128 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.14 [M + H]⁺ calcd for (d, J = 0.6 Hz, 1H), 8.49 (d, J = 7.9 Hz, C₂₁H₂₅FN₂O₅, 1H), 8.00 (d, J = 5.2 Hz, 1H), 7.18- 405.1820; found, 7.05 (m, 1H), 6.93-6.79 (m, 3H), 5.11 405.1819 (dq, J = 8.0, 6.3 Hz, 1H), 4.78-4.64 (m, 1H), 3.95 (s, 3H), 3.23-3.09 (m, 1H), 2.33 (s, 3H), 1.55 (d, J = 7.2 Hz, 3H), 1.24 (d, J = 6.9 Hz, 3H), 1.14 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.79, 168.69, 161.97, 160.03, 155.39, 148.77, 140.51, 137.87, 137.81, 137.33, 137.30, 130.47, 127.86, 127.79, 117.10, 116.94, 113.02, 112.85, 109.47, 76.32, 56.09, 48.13, 39.16, 20.00, 18.42, 18.36, 17.33. 129 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.09 [M + H]⁺ calcd for (s, 1H), 8.35 (d, J = 7.9 Hz, 1H), 7.98 C₂₁H₂₅FN₂O₅, (dd, J = 5.2, 3.6 Hz, 1H), 7.13 (dd, J = 405.1820; found, 8.4, 5.8 Hz, 1H), 6.94-6.73 (m, 3H), 405.1820 5.21-5.08 (m, 1H), 4.63-4.46 (m, 1H), 3.94 (s, 2H), 3.27-3.15 (m, 1H). ¹³C NMR (126 MHz, CDCl₃) δ 171.55, 168.59, 161.91, 159.97, 155.37, 148.73, 140.44, 138.30, 137.15, 130.43, 127.47, 116.73, 116.57, 112.89, 112.73, 109.43, 75.74, 56.07, 47.87, 38.98, 19.90, 17.79, 17.32. 130 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.11 [M + H]⁺ calcd for (s, 1H), 8.36 (d, J = 8.0 Hz, 1H), 7.97 C₂₁H₂₆N₂O₅, (d, J = 5.2 Hz, 1H), 7.24-7.01 (m, 387.1914; found, 4H), 6.86 (d, J = 5.2 Hz, 1H), 5.27- 387.1911 5.12 (m, 1H), 4.59-4.47 (m, 1H), 3.94 (s, 2H), 3.33-3.20 (m, 1H), 2.36 (s, 3H), 1.32 (d, J = 6.3 Hz, 3H), 1.24 (d, J = 7.1 Hz, 3H), 1.08 (d, J = 7.2 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.58, 168.54, 155.33, 148.71, 141.47, 140.41, 135.95, 130.49, 130.22, 126.20, 125.88, 109.39, 75.87, 56.06, 47.85, 39.52, 19.83, 17.83, 17.74, 17.14. 131 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.14 [M + H]⁺ calcd for (s, 1H), 8.47 (d, J = 8.0 Hz, 1H), 8.00 C₂₀H₂₃FN₂O₅, (d, J = 5.2 Hz, 1H), 7.15 (dd, J = 8.6, 391.1664; found, 5.4 Hz, 2H), 6.97 (t, J = 8.7 Hz, 2H), 391.1662 6.88 (d, J = 5.2 Hz, 1H), 5.11-5.02 (m, 1H), 4.71 (p, J = 7.3 Hz, 1H), 3.95 (s, 3H), 2.92 (p, J = 7.1 Hz, 1H), 1.53 (d, J = 7.2 Hz, 3H), 1.29 (d, J = 7.1 Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.67, 168.69, 162.64, 160.70, 155.40, 148.78, 140.51, 138.48, 130.46, 129.26, 129.19, 115.32, 115.16, 109.48, 76.31, 56.09, 48.12, 44.11, 18.38, 17.95, 17.16. 132 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.16 [M + H]⁺ calcd for (s, 1H), 8.51 (d, J = 7.9 Hz, 1H), 8.00 C₂₂H₂₈N₂O₆, (d, J = 5.2 Hz, 1H), 7.11-7.05 (m, 417.2020; found, 1H), 6.88 (d, J = 5.2 Hz, 1H), 6.70 (d, 417.2007 J = 6.7 Hz, 2H), 5.11 (dq, J = 8.3, 6.3 Hz, 1H), 4.72 (p, J = 7.3 Hz, 1H), 3.95 (s, 3H), 3.77 (s, 3H), 3.18-3.06 (m, 1H), 2.32 (s, 3H), 1.56 (d, J = 7.2 Hz, 3H), 1.23 (d, J = 6.9 Hz, 3H), 1.14 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.85, 168.67, 157.70, 155.38, 148.77, 140.50, 136.91, 133.86, 130.52, 127.36, 115.95, 111.48, 109.45, 56.08, 55.13, 48.17, 39.11, 20.18, 18.46, 17.57, 16.10. 133 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.14 [M + H]⁺ calcd for (s, 1H), 8.47 (d, J = 8.0 Hz, 1H), 8.01 C₂₁H₂₅FN₂O₅, (d, J = 5.2 Hz, 1H), 7.13 (dd, J = 9.4, 405.1820; found, 5.8 Hz, 1H), 6.91-6.81 (m, 3H), 5.12 405.1819 (dq, J = 8.1, 6.3 Hz, 1H), 4.72 (p, J = 7.2 Hz, 1H), 3.95 (s, 3H), 3.20-3.10 (m, 1H), 2.33 (s, 3H), 1.54 (d, J = 7.1 Hz, 3H), 1.23 (d, J = 6.9 Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.81, 168.74, 161.95, 160.01, 155.40, 148.78, 140.51, 137.89, 137.83, 137.29, 137.26, 130.48, 127.87, 127.81, 117.08, 116.91, 113.06, 112.90, 109.48, 76.19, 56.09, 47.96, 39.12, 20.02, 18.24, 18.12, 17.47. 134 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.12 [M + H]⁺ calcd for (s, 1H), 8.28 (d, J = 8.0 Hz, 1H), 7.99 C₂₁H₂₅FN₂O₅, (d, J = 5.2 Hz, 1H), 7.18-7.12 (m, 405.1820; found, 1H), 6.88 (d, J = 5.2 Hz, 1H), 6.78 (t, 405.1818 J = 8.2 Hz, 2H), 5.17-5.06 (m, 1H), 4.64-4.51 (m, 1H), 3.95 (s, 3H), 3.23 (p, J = 7.1 Hz, 1H), 2.33 (s, 3H), 1.38 (d, J = 7.1 Hz, 3H), 1.26-1.20 (m, 6H). ¹³C NMR (126 MHz, CDCl₃) δ 171.29, 168.55, 161.93, 159.99, 155.38, 148.74, 140.44, 138.41, 138.35, 136.73, 136.71, 130.43, 127.71, 127.65, 116.77, 116.61, 112.81, 112.64, 109.45, 75.62, 56.09, 47.82, 38.64, 19.89, 19.88, 18.06, 17.22, 16.84. 135 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.15 [M + H]⁺ calcd for (s, 1H), 8.30 (d, J = 8.0 Hz, 1H), 7.99 C₂₁H₂₆N₂O₅, (d, J = 5.2 Hz, 1H), 7.21 (dd, J = 7.8, 387.1914; found, 1.4 Hz, 1H), 7.15-7.00 (m, 3H), 6.87 387.1915 (d, J = 5.2 Hz, 1H), 5.20-5.12 (m, 1H), 4.59-4.50 (m, 1H), 3.95 (s, 3H), 3.29 (p, J = 7.1 Hz, 1H), 2.36 (s, 3H), 1.35 (d, J = 7.2 Hz, 3H), 1.29-1.22 (m, 6H). ¹³C NMR (126 MHz, CDCl₃) δ 171.30, 168.54, 155.35, 148.73, 141.04, 140.40, 136.09, 130.51, 130.26, 126.23, 126.11, 109.40, 75.73, 56.08, 47.88, 39.15, 19.83, 18.11, 17.16, 16.53. 136 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.14 [M + H]⁺ calcd for (s, 1H), 8.46 (d, J = 7.7 Hz, 1H), 8.00 C₂₀H₂₃FN₂O₅, (dd, J = 5.2, 2.2 Hz, 1H), 7.15 (ddd, 391.1664; found, J = 9.9, 6.1, 3.4 Hz, 2H), 6.97 (td, J = 391.1658 8.8, 2.6 Hz, 2H), 6.88 (dd, J = 5.4, 1.5 Hz, 1H), 5.12-5.01 (m, 1H), 4.77- 4.64 (m, 1H), 3.95 (s, 3H), 2.92 (p, J = 7.1 Hz, 1H), 1.53 (d, J = 7.2 Hz, 3H), 1.28 (d, J = 7.0 Hz, 3H), 1.09 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.72, 168.76, 162.65, 160.70, 155.41, 148.78, 140.51, 138.43, 138.40, 130.47, 129.29, 129.23, 115.33, 115.16, 109.48, 76.12, 56.09, 47.98, 44.09, 18.20, 17.69, 17.30. 137 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.17 [M + H]⁺ calcd for (s, 1H), 8.50 (d, J = 7.9 Hz, 1H), 8.01 C₂₂H₂₈N₂O₆, (d, J = 5.2 Hz, 1H), 7.09 (d, J = 8.4 Hz, 417.2020; found, 1H), 6.88 (d, J = 5.2 Hz, 1H), 6.76- 417.2010 6.67 (m, 2H), 5.13 (dq, J = 8.3, 6.3 Hz, 1H), 4.72 (p, J = 7.3 Hz, 1H), 3.95 (s, 3H), 3.76 (s, 3H), 3.18-3.07 (m, 1H), 2.32 (s, 3H), 1.54 (d, J = 7.2 Hz, 3H), 1.23 (d, J = 6.9 Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.86, 168.72, 157.68, 155.38, 148.76, 140.50, 136.94, 133.82, 130.53, 127.37, 115.97, 111.47, 109.45, 76.65, 56.08, 55.11, 47.99, 39.06, 20.19, 18.31, 18.20, 17.68. 139 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.12 [M + H]⁺ calcd for (s, 1H), 8.38 (d, J = 9.3 Hz, 1H), 7.99 C₂₃H₂₉FN₂O₅, (t, J = 5.1 Hz, 1H), 7.14 (dd, J = 8.5, 433.2133; found, 5.9 Hz, 1H), 6.88 (dd, J = 7.6, 5.1 Hz, 433.213 1H), 6.84-6.72 (m, 3H), 5.13 (dq, J = 8.4, 6.3 Hz, 1H), 4.49 (td, J = 9.4, 4.9 Hz, 1H), 3.94 (s, 3H), 3.20 (p, J = 7.4 Hz, 1H), 2.33 (s, 3H), 1.94 (pd, J = 6.9, 4.6 Hz, 1H), 1.29 (d, J = 6.3 Hz, 3H), 1.21 (d, J = 7.1 Hz, 3H), 0.85 (d, J = 6.9 Hz, 3H), 0.68 (d, J = 6.8 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 170.52, 168.98, 161.96, 160.02, 155.39, 148.70, 140.45, 138.31, 138.25, 137.28, 137.25, 130.49, 127.46, 127.40, 116.75, 116.59, 112.92, 112.76, 109.42, 75.86, 56.97, 56.08, 38.86, 31.12, 19.89, 19.12, 17.79, 17.34, 17.02. 140 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.38 (d, [M + H]⁺ calcd for J = 9.4 Hz, 1H), 7.99 (d, J = 5.2 Hz, C₂₃H₃₀N₂O₅, 1H), 7.20 (d, J = 7.7 Hz, 1H), 7.16- 415.2227; found, 7.08 (m, 1H), 7.08-7.03 (m, 2H), 6.86 415.2222 (d, J = 5.2 Hz, 1H), 5.25-5.11 (m, 1H), 4.49 (dd, J = 9.4, 4.5 Hz, 1H), 3.94 (s, 3H), 3.37-3.18 (m, 1H), 2.34 (s, 3H), 1.91 (pd, J = 6.9, 4.5 Hz, 1H), 1.31 (d, J = 6.2 Hz, 3H), 1.23 (d, J = 7.1 Hz, 3H), 0.82 (d, J = 6.8 Hz, 3H), 0.64 (d, J = 6.8 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 170.54, 168.94, 155.34, 148.67, 141.56, 140.42, 135.94, 130.56, 130.25, 126.23, 125.89, 109.37, 75.96, 56.90, 56.07, 39.37, 31.11, 19.82, 19.14, 17.78, 17.11, 16.98. 141 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.16 [M + H]⁺ calcd for (s, 1H), 8.48 (d, J = 9.4 Hz, 1H), 8.01 C₂₂H₂₇FN₂O₅, (d, J = 5.2 Hz, 1H), 7.19-7.10 (m, 419.1977; found, 2H), 6.94 (t, J = 8.7 Hz, 2H), 6.89 (d, 419.1973 J = 5.2 Hz, 1H), 5.11-4.98 (m, 1H), 4.64 (dd, J = 9.4, 4.8 Hz, 1H), 3.95 (s, 3H), 2.92 (p, J = 7.1 Hz, 1H), 2.31 (pd, J = 6.9, 4.8 Hz, 1H), 1.29 (d, J = 7.0 Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H), 1.03 (d, J = 6.8 Hz, 3H), 0.95 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 170.57, 169.05, 162.62, 160.67, 155.43, 148.76, 140.52, 138.50, 130.50, 129.23, 129.16, 115.29, 115.13, 109.47, 77.27, 76.39, 57.25, 56.10, 43.96, 31.33, 19.41, 18.04, 17.40, 17.07. 142 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.18 [M + H]⁺ calcd for (s, 1H), 8.52 (d, J = 9.4 Hz, 1H), 8.02 C₂₄H₃₂N₂O₆, (d, J = 5.2 Hz, 1H), 7.06 (d, J = 8.4 Hz, 445.2333; found, 1H), 6.88 (d, J = 5.2 Hz, 1H), 6.75- 445.2314 6.63 (m, 2H), 5.08 (dq, J = 8.3, 6.2 Hz, 1H), 4.66 (dd, J = 9.4, 4.8 Hz, 1H), 3.95 (s, 3H), 3.76 (s, 3H), 3.19-3.06 (m, 1H), 2.41-2.33 (m, 1H), 2.31 (s, 3H), 1.23 (d, J = 6.9 Hz, 3H), 1.13 (d, J = 6.2 Hz, 3H), 1.05 (d, J = 6.9 Hz, 3H), 0.98 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 170.79, 169.06, 157.68, 155.40, 148.74, 140.51, 136.87, 133.93, 130.56, 127.33, 115.96, 111.46, 109.44, 76.90, 57.29, 56.08, 55.12, 39.01, 31.37, 20.17, 19.50, 18.52, 17.65, 17.40. 143 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.18 [M + H]⁺ calcd for (s, 1H), 8.50 (d, J = 9.2 Hz, 1H), 8.02 C₂₃H₂₉FN₂O₅, (d, J = 5.2 Hz, 1H), 7.13 (dd, J = 9.5, 433.2133; found, 5.7 Hz, 1H), 6.89 (d, J = 5.2 Hz, 1H), 433.2142 6.87-6.82 (m, 2H), 5.12 (dq, J = 8.0, 6.3 Hz, 1H), 4.63 (dd, J = 9.3, 5.1 Hz, 1H), 3.95 (s, 3H), 3.15 (p, J = 7.1 Hz, 1H), 2.41-2.25 (m, 4H), 1.24 (d, J = 6.9 Hz, 3H), 1.13 (d, J = 6.3 Hz, 3H), 1.03 (d, J = 6.9 Hz, 3H), 0.99 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 170.87, 169.06, 161.95, 160.01, 155.41, 148.74, 140.53, 137.86, 137.80, 137.31, 137.28, 130.54, 127.91, 117.05, 116.89, 113.06, 112.89, 109.46, 76.09, 57.04, 56.09, 39.11, 31.39, 20.00, 19.12, 18.25, 17.80, 17.41. 144 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.16 [M + H]⁺ calcd for (s, 1H), 8.32 (d, J = 9.2 Hz, 1H), 8.00 C₂₃H₂₉FN₂O₅, (d, J = 5.2 Hz, 1H), 7.16 (dd, J = 8.4, 433.2133; found, 5.8 Hz, 1H), 6.89 (d, J = 5.2 Hz, 1H), 433.2139 6.78 (ddd, J = 9.8, 7.0, 4.1 Hz, 2H), 5.17-5.05 (m, 1H), 4.48 (dd, J = 9.3, 5.3 Hz, 1H), 3.96 (s, 3H), 3.22 (p, J = 7.2 Hz, 1H), 2.33 (s, 3H), 2.18 (pd, J = 6.9, 5.2 Hz, 1H), 1.28-1.19 (m, 6H), 0.92 (d, J = 6.8 Hz, 3H), 0.86 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 170.29, 168.86, 161.96, 160.02, 155.40, 148.71, 140.46, 138.45, 138.39, 136.79, 136.76, 130.49, 127.77, 127.70, 116.77, 116.61, 112.79, 112.63, 109.43, 75.66, 57.06, 56.09, 38.58, 31.26, 19.91, 18.94, 17.61, 17.30, 16.84. 145 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.19 [M + H]⁺ calcd for (s, 1H), 8.34 (d, J = 9.3 Hz, 1H), 8.00 C₂₃H₃₀N₂O₅, (d, J = 5.2 Hz, 1H), 7.21 (dd, J = 7.6, 415.2227; found, 1.7 Hz, 1H), 7.14-7.05 (m, 2H), 7.02 415.2224 (td, J = 7.2, 1.4 Hz, 1H), 6.88 (d, J = 5.2 Hz, 1H), 5.20-5.12 (m, 1H), 4.48 (dd, J = 9.3, 5.1 Hz, 1H), 3.95 (s, 3H), 3.28 (p, J = 7.1 Hz, 1H), 2.36 (s, 3H), 2.17 (pd, J = 6.9, 5.1 Hz, 1H), 1.29- 1.22 (m, 6H), 0.90 (d, J = 6.8 Hz, 3H), 0.84 (d, J = 6.8 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 170.28, 168.84, 155.36, 148.69, 141.08, 140.42, 136.11, 130.59, 130.28, 126.23, 126.11, 109.39, 75.76, 57.06, 56.08, 39.06, 31.33, 19.83, 18.93, 17.59, 17.20, 16.50. 146 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.17 [M + H]⁺ calcd for (s, 1H), 8.50 (d, J = 8.9 Hz, 1H), 8.02 C₂₂H₂₇FN₂O₅, (d, J = 5.2 Hz, 1H), 7.19-7.10 (m, 419.1977; found, 3H), 7.00-6.93 (m, 2H), 6.89 (d, J = 419.1974 5.2 Hz, 1H), 5.11-5.02 (m, 1H), 4.67- 4.58 (m, 1H), 3.95 (s, 4H), 2.92 (p, J = 7.1 Hz, 1H), 2.31 (pd, J = 6.9, 5.0 Hz, 1H), 1.28 (d, J = 7.0 Hz, 3H), 1.10 (d, J = 6.2 Hz, 3H), 1.02 (d, J = 6.9 Hz, 3H), 0.99 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 170.76, 169.06, 162.64, 160.70, 155.41, 148.74, 140.53, 138.48, 130.53, 129.28, 129.22, 115.33, 115.16, 109.46, 76.11, 57.07, 56.09, 44.09, 31.35, 19.09, 17.87, 17.82, 17.23. 147 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.20 [M + H]⁺ calcd for (s, 1H), 8.53 (d, J = 9.2 Hz, 1H), 8.02 C₂₄H₃₂N₂O₆, (d, J = 5.2 Hz, 1H), 7.10 (d, J = 8.4 Hz, 445.2333; found, 1H), 6.88 (d, J = 5.2 Hz, 1H), 6.75- 445.2334 6.64 (m, 2H), 5.12 (dq, J = 8.2, 6.3 Hz, 1H), 4.65 (dd, J = 9.2, 5.0 Hz, 1H), 3.95 (s, 3H), 3.75 (s, 3H), 3.20-3.06 (m, 1H), 2.32 (s, 4H), 1.23 (d, J = 6.9 Hz, 3H), 1.13 (d, J = 6.2 Hz, 3H), 1.03 (d, J = 6.9 Hz, 3H), 1.00 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 170.92, 169.04, 157.67, 155.39, 148.73, 140.52, 136.92, 133.85, 130.59, 127.40, 116.00, 111.44, 109.43, 76.56, 57.04, 56.08, 55.10, 39.05, 31.44, 20.18, 19.13, 18.32, 17.80, 17.65. 148 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.14 [M + H]⁺ calcd for (s, 1H), 8.47 (d, J = 7.9 Hz, 1H), 8.01 C₂₁H₂₅FN₂O₅, (d, J = 5.2 Hz, 1H), 7.13 (dd, J = 9.5, 405.1820; found, 5.8 Hz, 1H), 6.91-6.80 (m, 3H), 5.12 405.1820 (dq, J = 8.1, 6.3 Hz, 1H), 4.72 (p, J = 7.3 Hz, 1H), 3.95 (s, 3H), 3.21-3.10 (m, 1H), 2.33 (s, 3H), 1.54 (d, J = 7.2 Hz, 3H), 1.23 (d, J = 6.9 Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.81, 168.74, 161.95, 160.01, 155.40, 148.78, 140.51, 137.89, 137.83, 137.29, 137.26, 130.48, 127.87, 127.81, 117.07, 116.91, 113.06, 112.90, 109.48, 76.19, 56.09, 47.96, 39.12, 20.01, 18.24, 18.13, 17.48. 149 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.12 [M + H]⁺ calcd for (s, 1H), 8.28 (d, J = 8.0 Hz, 1H), 7.99 C₂₁H₂₅FN₂O₅, (d, J = 5.2 Hz, 1H), 7.22-7.09 (m, 405.1820; found, 1H), 6.88 (d, J = 5.2 Hz, 1H), 6.83- 405.1820 6.74 (m, 2H), 5.19-5.06 (m, 1H), 4.62-4.50 (m, 1H), 3.95 (s, 3H), 3.31- 3.17 (m, 1H), 2.33 (s, 3H), 1.38 (d, J = 7.2 Hz, 3H), 1.27-1.18 (m, 6H). ¹³C NMR (126 MHz, CDCl₃) δ 171.29, 168.55, 161.93, 159.99, 155.38, 148.74, 140.44, 138.41, 138.35, 136.73, 136.71, 130.43, 127.71, 127.64, 116.77, 116.61, 112.80, 112.64, 109.45, 75.62, 56.09, 47.82, 38.64, 18.06, 17.22, 16.84. 150 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.15 [M + H]⁺ calcd for (s, 1H), 8.30 (d, J = 7.9 Hz, 1H), 7.99 C₂₁H₂₆N₂O₅, (d, J = 5.2 Hz, 1H), 7.21 (dd, J = 7.8, 387.1914; found, 1.4 Hz, 1H), 7.15-7.01 (m, 4H), 6.87 387.1913 (d, J = 5.2 Hz, 1H), 5.23-5.08 (m, 1H), 4.58-4.49 (m, 1H), 3.95 (s, 3H), 3.28 (h, J = 7.3 Hz, 1H), 2.36 (s, 3H), 1.35 (d, J = 7.2 Hz, 3H), 1.28-1.22 (m, 6H). ¹³C NMR (126 MHz, CDCl₃) δ 171.29, 168.54, 155.35, 148.73, 141.04, 140.40, 136.09, 130.51, 130.26, 126.23, 126.11, 109.40, 75.73, 56.08, 47.88, 39.15, 19.83, 18.11, 17.16, 16.53. 151 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.14 [M + H]⁺ calcd for (d, J = 0.6 Hz, 1H), 8.46 (d, J = 7.9 Hz, C₂₀H₂₃FN₂O₅, 1H), 8.01 (d, J = 5.2 Hz, 1H), 7.16 (dd, 391.1664; found, J = 8.7, 5.4 Hz, 2H), 6.97 (t, J = 8.7 391.1658 Hz, 2H), 6.88 (d, J = 5.2 Hz, 1H), 5.07 (dq, J = 7.4, 6.3 Hz, 1H), 4.79-4.64 (m, 1H), 3.95 (s, 3H), 2.92 (p, J = 7.1 Hz, 1H), 1.53 (d, J = 7.2 Hz, 3H), 1.28 (d, J = 7.1 Hz, 3H), 1.09 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.72, 168.76, 162.65, 160.70, 155.40, 148.78, 140.51, 138.43, 130.47, 129.29, 129.23, 115.33, 115.16, 109.48, 76.12, 56.09, 47.98, 44.09, 18.19, 17.69, 17.30. 152 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.17 [M + H]⁺ calcd for (s, 1H), 8.50 (d, J = 7.9 Hz, 1H), 8.01 C₂₂H₂₈N₂O₆, (d, J = 5.2 Hz, 1H), 7.09 (d, J = 8.3 Hz, 417.2020; found, 1H), 6.88 (d, J = 5.2 Hz, 1H), 6.78- 417.2007 6.64 (m, 2H), 5.13 (dq, J = 8.4, 6.3 Hz, 1H), 4.73 (p, J = 7.3 Hz, 1H), 3.95 (s, 3H), 3.76 (s, 3H), 3.18-3.06 (m, 1H), 2.32 (s, 3H), 1.54 (d, J = 7.2 Hz, 3H), 1.23 (d, J = 6.9 Hz, 3H), 1.12 (d, J = 6.2 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.86, 168.72, 157.68, 155.38, 148.76, 140.50, 136.94, 133.81, 130.53, 127.37, 115.97, 111.47, 109.45, 76.65, 56.08, 55.11, 47.99, 39.06, 20.19, 18.30, 18.19, 17.68. 153 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.14 [M + H]⁺ calcd for (s, 1H), 8.49 (d, J = 8.0 Hz, 1H), 8.00 C₂₁H₂₅FN₂O₅, (d, J = 5.2 Hz, 1H), 7.17-7.08 (m, 405.1820; found, 1H), 6.91-6.81 (m, 4H), 5.11 (dq, J = 405.1818 8.1, 6.3 Hz, 1H), 4.72 (p, J = 7.3 Hz, 1H), 3.95 (s, 3H), 3.20-3.10 (m, 1H), 2.33 (s, 3H), 1.55 (d, J = 7.2 Hz, 3H), 1.24 (d, J = 6.9 Hz, 3H), 1.14 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.80, 168.69, 161.97, 160.03, 155.39, 148.77, 140.51, 137.87, 137.81, 137.33, 137.30, 130.47, 127.86, 127.79, 117.10, 116.94, 113.02, 112.86, 109.47, 76.33, 56.09, 48.13, 39.16, 20.00, 18.41, 18.36, 17.33. 154 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.09 [M + H]⁺ calcd for (s, 1H), 8.35 (d, J = 8.0 Hz, 1H), 7.98 C₂₁H₂₅FN₂O₅, (d, J = 5.2 Hz, 1H), 7.13 (dd, J = 8.4, 405.1820; found, 5.8 Hz, 1H), 6.86 (d, J = 5.2 Hz, 1H), 405.1816 6.80 (ddd, J = 9.5, 7.0, 4.1 Hz, 2H), 5.14 (dq, J = 8.2, 6.2 Hz, 1H), 4.60- 4.49 (m, 1H), 3.94 (s, 3H), 3.27-3.16 (m, 1H), 2.34 (s, 3H), 1.30 (d, J = 6.3 Hz, 3H), 1.22 (d, J = 7.1 Hz, 3H), 1.14 (d, J = 7.2 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.55, 168.59, 161.91, 159.97, 155.37, 148.74, 140.44, 138.30, 138.24, 137.15, 137.13, 130.43, 127.46, 127.40, 116.74, 116.57, 112.90, 112.73, 109.43, 75.74, 56.08, 47.87, 38.98, 19.90, 19.89, 17.79, 17.32. 155 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.11 [M + H]⁺ calcd for (d, J = 0.6 Hz, 1H), 8.36 (d, J = 8.0 Hz, C₂₁H₂₆N₂O₅, 1H), 7.97 (d, J = 5.2 Hz, 1H), 7.19 (dd, 387.1914; found, J = 7.5, 1.2 Hz, 1H), 7.12 (td, J = 7.8, 387.1912 7.0, 2.4 Hz, 1H), 7.09-7.02 (m, 2H), 6.86 (d, J = 5.2 Hz, 1H), 5.19 (dq, J = 8.3, 6.2 Hz, 1H), 4.60-4.45 (m, 1H), 3.94 (s, 3H), 3.33-3.20 (m, 1H), 2.36 (s, 3H), 1.32 (d, J = 6.2 Hz, 3H), 1.24 (d, J = 7.0 Hz, 3H), 1.08 (d, J = 7.2 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.58, 168.54, 155.33, 148.71, 141.47, 140.41, 135.95, 130.49, 130.22, 126.20, 125.88, 109.39, 75.87, 56.06, 47.85, 39.52, 19.83, 17.83, 17.74, 17.14. 156 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.14 [M + H]⁺ calcd for (s, 1H), 8.47 (d, J = 7.7 Hz, 1H), 8.00 C₂₀H₂₃FN₂O₅, (d, J = 5.2 Hz, 1H), 7.21-7.10 (m, 391.1664; found, 3H), 6.97 (td, J = 8.8, 2.6 Hz, 2H), 6.88 391.1661 (dd, J = 5.3, 1.7 Hz, 1H), 5.12-5.01 (m, 1H), 4.77-4.66 (m, 1H), 3.95 (d, J = 1.6 Hz, 4H), 2.92 (p, J = 7.1 Hz, 1H), 1.53 (d, J = 7.2 Hz, 4H), 1.29 (d, J = 7.0 Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.67, 168.69, 162.64, 160.70, 155.40, 148.78, 140.51, 138.45, 130.46, 129.26, 115.32, 115.16, 109.48, 76.31, 56.09, 48.12, 44.11, 18.38, 17.95, 17.16. 157 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.16 [M + H]⁺ calcd for (s, 1H), 8.51 (d, J = 7.9 Hz, 1H), 8.00 C₂₂H₂₈N₂O₆, (d, J = 5.2 Hz, 1H), 7.12-7.06 (m, 417.2020; found, 1H), 6.88 (d, J = 5.2 Hz, 1H), 6.76- 417.2006 6.67 (m, 2H), 5.11 (dq, J = 8.3, 6.3 Hz, 1H), 4.72 (p, J = 7.3 Hz, 1H), 3.95 (s, 3H), 3.77 (s, 3H), 3.19-3.07 (m, 1H), 2.32 (s, 3H), 1.61-1.51 (m, 4H), 1.23 (d, J = 6.9 Hz, 3H), 1.14 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.86, 168.68, 157.70, 155.38, 148.77, 140.50, 136.91, 133.86, 130.51, 127.36, 115.95, 111.48, 109.45, 56.08, 55.13, 48.17, 39.11, 20.18, 18.46, 17.57. 158 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 12.13 film) 3369, [M + H]⁺ calcd for (s, 1H), 8.58-8.47 (m, 1H), 8.01 (d, 2983, 1736, C₂₁H₂₄F₃N₂O₅, J = 5.2 Hz, 1H), 7.68-7.61 (m, 1H), 1649, 1528, 441.1632; found, 7.51 (td, J = 7.7, 1.2 Hz, 1H), 7.43 (d, 1310, 1148, 441.1627 J = 7.7 Hz, 1H), 7.38-7.29 (m, 1H), 1115, 770, 6.88 (d, J = 5.2 Hz, 1H), 5.29-5.15 731 cm⁻¹ (m, 1H), 4.82-4.71 (m, 1H), 3.95 (s, 3H), 3.42-3.29 (m, 1H), 1.60 (d, J = 7.2 Hz, 3H), 1.29 (d, J = 6.8 Hz, 3H), 1.12 (d, J = 6.2 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −58.24. 159 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 12.11 film) 3370, [M + H]⁺ calcd for (s, 1H), 8.50 (d, J = 7.9 Hz, 1H), 8.01 2984, 1737, C₂₁H₂₃F₄N₂O₅, (d, J = 5.2 Hz, 1H), 7.42 (dd, J = 8.8, 1528, 1313, 459.1538; found, 5.3 Hz, 1H), 7.35 (dd, J = 9.2, 2.8 Hz, 1151, 1118, 459.1535 1H), 7.21 (td, J = 8.2, 2.8 Hz, 1H), 6.89 1045, 908, (d, J = 5.2 Hz, 1H), 5.24-5.09 (m, 799, 738 1H), 4.82-4.67 (m, 1H), 3.95 (s, 3H), cm⁻¹ 3.41-3.26 (m, 1H), 1.59 (d, J = 7.2 Hz, 3H), 1.27 (d, J = 6.8 Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −58.78, −113.91. 160 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 12.17 film) 3369, [M + H]⁺ calcd for (s, 1H), 8.53 (d, J = 7.8 Hz, 1H), 7.99 2944, 1732, C₁₉H₂₉N₂O₅, (d, J = 5.2 Hz, 1H), 6.87 (d, J = 5.2 Hz, 1648, 1526, 365.2071; found, 1H), 5.11 (qd, J = 6.4, 3.1 Hz, 1H), 1438, 1280, 365.2067 4.76-4.64 (m, 1H), 3.95 (s, 3H), 1.76 1263, 1216, (dddd, J = 13.2, 10.4, 8.0, 6.4 Hz, 2H), 1149, 1057, 1.69-1.52 (m, 6H), 1.52-1.43 (m, 800 cm⁻¹ 1H), 1.43-1.35 (m, 1H), 1.24 (d, J = 6.4 Hz, 3H), 1.19-0.98 (m, 3H), 0.98- 0.89 (m, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 171.76, 168.71, 155.39, 148.78, 140.46, 130.58, 109.43, 74.81, 56.08, 48.23, 43.31, 43.13, 31.22, 30.74, 25.15, 24.98, 18.51, 17.78, 12.50. 161 HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 12.15 [M + H]⁺ calcd for (s, 1H), 8.48 (d, J = 8.0 Hz, 1H), 8.01 C₂₁H₂₄F₃N₂O₅, (d, J = 5.2 Hz, 1H), 7.64 (dd, J = 7.9, 441.1632; found, 1.3 Hz, 1H), 7.56-7.47 (m, 1H), 7.44 441.1624 (d, J = 7.8 Hz, 1H), 7.31 (t, J = 7.5 Hz, 1H), 6.88 (d, J = 5.2 Hz, 1H), 5.27- 5.17 (m, 1H), 4.83-4.68 (m, 1H), 3.95 (s, 3H), 3.42-3.28 (m, 1H), 1.58 (d, J = 7.2 Hz, 3H), 1.30 (d, J = 6.8 Hz, 3H), 1.10 (d, J = 6.2 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −58.24. 162 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 12.12 film) 2983, [M + H]⁺ calcd for (s, 1H), 8.46 (d, J = 7.9 Hz, 1H), 8.01 1738, 1649, C₂₁H₂₃F₄N₂O₅, (d, J = 5.2 Hz, 1H), 7.43 (dd, J = 8.8, 1528, 1313, 459.1538; found, 5.3 Hz, 1H), 7.34 (dd, J = 9.2, 2.8 Hz, 1152, 1119, 459.1530 1H), 7.21 (td, J = 8.2, 2.8 Hz, 1H), 6.89 1045, 909, (d, J = 5.2 Hz, 1H), 5.18 (p, J = 6.6 Hz, 800, 732 1H), 4.79-4.69 (m, 1H), 3.95 (s, 3H), cm⁻¹ 3.31 (p, J = 7.1 Hz, 1H), 1.57 (d, J = 7.2 Hz, 3H), 1.29 (d, J = 6.9 Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −58.78, −114.01. 163 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 12.18 film) 3370, [M + H]⁺ calcd for (s, 1H), 8.52 (d, J = 7.8 Hz, 1H), 7.99 2944, 1732, C₁₉H₂₉N₂O₅, (d, J = 5.2 Hz, 1H), 6.87 (d, J = 5.2 Hz, 1649, 1526, 365.2071; found, 1H), 5.10 (qd, J = 6.4, 3.0 Hz, 1H), 1438, 1263, 365.2068 4.74-4.64 (m, 1H), 3.95 (s, 3H), 1.83- 1216, 1150, 1.65 (m, 3H), 1.65-1.52 (m, 6H), 1058, 954, 1.52-1.34 (m, 2H), 1.23 (d, J = 6.4 800, 731 Hz, 3H), 1.18-1.03 (m, 2H), 0.94 (d, cm⁻¹ J = 6.9 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 171.75, 168.76, 155.39, 148.79, 140.46, 130.62, 109.44, 74.90, 56.08, 48.04, 43.11, 42.95, 31.26, 30.67, 25.14, 25.00, 18.33, 17.49, 12.53. 164 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 12.17 film) 3369, [M + H]⁺ calcd for (s, 1H), 8.58 (t, J = 7.7 Hz, 1H), 7.99 2971, 1733, C₂₂H₂₉N₂O₅, (d, J = 5.2 Hz, 1H), 7.14-6.90 (m, 1648, 1527, 401.2071; found, 3H), 6.87 (d, J = 5.3 Hz, 1H), 5.72- 1438, 1263, 401.2072 5.58 (m, 1H), 4.86-4.71 (m, 1H), 3.93 1149, 1057, (s, 3H), 3.44 (dp, J = 10.5, 7.1 Hz, 1H), 801, 770, 2.42 (d, J = 1.7 Hz, 3H), 2.38 (s, 3H), 730 cm⁻¹ 1.61 (dd, J = 14.3, 7.2 Hz, 3H), 1.29 (dd, J = 7.1, 2.7 Hz, 3H), 1.10-0.95 (m, 3H). 165 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 12.15 film) 3370, [M + H]⁺ calcd for (s, 1H), 8.69-8.42 (m, 1H), 8.00 (d, 2975, 1734, C₂₂H₂₈FN₂O₅, J = 5.2 Hz, 1H), 6.88 (d, J = 5.2 Hz, 1H), 1649, 1527, 419.1977; found, 6.70 (ddd, J = 14.6, 8.1, 2.5 Hz, 2H), 1480, 1262, 419.1975 5.59 (ddq, J = 12.4, 10.7, 6.2 Hz, 1H), 1148, 849, 4.76 (p, J = 7.2 Hz, 1H), 3.94 (d, J = 799, 728 1.9 Hz, 3H), 3.38 (dp, J = 10.5, 7.0 Hz, cm⁻¹ 1H), 2.41 (d, J = 1.9 Hz, 3H), 2.36 (s, 3H), 1.61 (dd, J = 13.6, 7.2 Hz, 3H), 1.27 (dd, J = 7.1, 3.1 Hz, 3H), 1.04 (dt, J = 11.6, 6.2 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −118.25, −118.31. 166 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 12.16 film) 3369, [M + H]⁺ calcd for (d, J = 3.9 Hz, 1H), 8.56 (t, J = 7.7 Hz, 2971, 1733, C₂₂H₂₉N₂O₅, 1H), 8.00 (d, J = 5.2 Hz, 1H), 7.07- 1648, 1527, 401.2071; found, 6.90 (m, 3H), 6.88 (d, J = 5.2 Hz, 1H), 1438, 1280, 401.2066 5.73-5.53 (m, 1H), 4.76 (pd, J = 7.2, 1263, 1149, 1.1 Hz, 1H), 3.95 (s, 3H), 3.43 (dp, J = 1056, 801, 10.5, 7.2 Hz, 1H), 2.42 (d, J = 1.9 Hz, 770, 730 3H), 2.38 (s, 3H), 1.61 (dd, J = 14.3, cm⁻¹ 7.2 Hz, 3H), 1.29 (dd, J = 7.2, 2.3 Hz, 3H), 1.06 (t, J = 6.0 Hz, 3H). 167 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 12.15 film) 3370, [M + H]⁺ calcd for (d, J = 3.3 Hz, 1H), 8.55 (t, J = 7.9 Hz, 2976, 1734, C₂₂H₂₈FN₂O₅, 1H), 8.00 (d, J = 5.2 Hz, 1H), 6.88 (d, 1649, 1527, 419.1977; found, J = 5.2 Hz, 1H), 6.70 (ddd, J = 15.1, 9.4, 1480, 1263, 419.1971 2.6 Hz, 2H), 5.59 (ddq, J = 12.4, 10.5, 1149, 849, 6.2 Hz, 1H), 4.76 (p, J = 7.3 Hz, 1H), 800, 730 3.95 (s, 3H), 3.38 (dp, J = 10.5, 7.0 Hz, cm⁻¹ 1H), 2.41 (d, J = 1.9 Hz, 3H), 2.36 (s, 3H), 1.61 (dd, J = 13.6, 7.2 Hz, 3H), 1.27 (dd, J = 7.2, 2.9 Hz, 3H), 1.05 (t, J = 5.9 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −118.26, −118.27, −118.33. 168 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 12.16 film) 3370, [M + H]⁺ calcd for (d, J = 3.8 Hz, 1H), 8.56 (t, J = 7.6 Hz, 2971, 1734, C₂₂H₂₉N₂O₅, 1H), 8.01 (d, J = 5.2 Hz, 1H), 7.05- 1649, 1527, 401.2071; found, 6.91 (m, 3H), 6.88 (d, J = 5.2 Hz, 1H), 1451, 1263, 401.2070 5.70-5.57 (m, 1H), 4.76 (pd, J = 7.1, 1150, 801, 1.1 Hz, 1H), 3.95 (s, 3H), 3.43 (dp, J = 770, 730 10.5, 7.2 Hz, 1H), 2.42 (d, J = 2.0 Hz, cm⁻¹ 3H), 2.38 (s, 3H), 1.61 (dd, J = 14.3, 7.2 Hz, 3H), 1.29 (dd, J = 7.2, 2.1 Hz, 3H), 1.06 (t, J = 6.0 Hz, 3H). 169 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 12.15 film) 3371, [M + H]⁺ calcd for (d, J = 3.3 Hz, 1H), 8.55 (t, J = 7.8 Hz, 2976, 1734, C₂₂H₂₈FN₂O₅, 1H), 8.00 (d, J = 5.2 Hz, 1H), 6.88 (d, 1649, 1527, 419.1977; found, J = 5.2 Hz, 1H), 6.70 (ddd, J = 17.0, 9.4, 1480, 1280, 419.1971 2.8 Hz, 2H), 5.59 (ddq, J = 12.2, 10.8, 1262, 1157, 6.2 Hz, 1H), 4.76 (p, J = 7.3 Hz, 1H), 849, 800, 3.95 (s, 3H), 3.38 (dp, J = 10.4, 7.0 Hz, 731 cm⁻¹ 1H), 2.41 (d, J = 2.2 Hz, 3H), 2.36 (s, 3H), 1.61 (dd, J = 13.6, 7.2 Hz, 3H), 1.27 (dd, J = 72, 2.8 Hz, 3H), 1.05 (t, J = 5.9 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −118.29, −118.36. 170 HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 12.16 [M + H]⁺ calcd for (s, 1H), 8.41 (d, J = 7.9 Hz, 1H), 7.97 C₂₁H₂₇N₂O₆, (d, J = 5.2 Hz, 1H), 7.23-7.10 (m, 403.1864; found, 2H), 6.92-6.78 (m, 3H), 5.31 (dq, J = 403.1827 7.8, 6.3 Hz, 1H), 4.63-4.49 (m, 1H), 3.93 (s, 3H), 3.81 (s, 3H), 3.49-3.39 (m, 1H), 1.26 (d, J = 6.3 Hz, 3H), 1.23 (d, J = 7.2 Hz, 3H), 1.16 (d, J = 7.2 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 171.5, 168.6, 157.2, 155.3, 148.7, 140.4, 131.1, 130.6, 128.1, 127.4, 120.5, 110.5, 109.4, 75.1, 56.0, 55.4, 48.0, 37.6, 17.9, 17.8, 16.6. 171 IR (thin HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.16 film) 2978, [M + H]⁺ calcd for (s, 1H), 8.50 (d, J = 8.0 Hz, 1H), 8.01 2937, 1733, C₂₀H₂₅N₂O₅, (d, J = 5.2 Hz, 1H), 7.32-7.27 (m, 1647, 1527, 373.1758; found, 2H), 7.24-7.16 (m, 3H), 6.88 (d, J = 1451, 1262, 373.1752 5.2 Hz, 1H), 5.11 (dq, J = 1.1, 6.3 Hz, 1147, 701 1H), 4.77-4.67 (m, 1H), 3.95 (s, 3H), cm⁻¹ 2.97-2.87 (m, 1H), 1.54 (d, J = 1.2 Hz, 3H), 1.31 (d, J = 7.0 Hz, 3H), 1.13 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.8, 168.7, 155.3, 148.7, 142.9, 140.5, 130.4, 128.5, 127.8, 126.8, 109.4, 76.5, 56.1, 48.1, 44.9, 18.4, 18.2, 17.2. 172 IR (thin HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.16 film) 3368, [M + H]⁺ calcd for (s, 1H), 8.50 (d, J = 7.9 Hz, 1H), 8.00 2978, 1937, C₁₉H₂₅N₂O₅S, (d, J = 5.2 Hz, 1H), 6.88 (d, J = 5.2 Hz, 1734, 1648, 393.1479; found, 1H), 6.61 (d, J = 3.5 Hz, 1H), 6.55 (dq, 1527, 1480, 393.1473 J = 3.5, 1.1 Hz, 1H), 5.10-5.01 (m, 1438, 1262, 1H), 4.77-4.67 (m, 1H), 3.95 (s, 3H), 797, 730 3.22-3.12 (m, 1H), 2.42 (d, J = 1.1 cm⁻¹ Hz, 3H), 1.55 (d, J = 7.1 Hz, 3H), 1.33 (d, J = 7.0 Hz, 3H), 1.20 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.6, 168.7, 155.3, 148.7, 143.3, 140.5, 138.0, 130.5, 124.5, 124.1, 109.4, 76.1, 56.1, 48.1, 40.1, 18.4, 17.8, 17.2, 15.3. 173 IR (thin HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 12.19 film) 3369, [M + H]⁺ calcd for (s, 1H), 8.49 (d, J = 7.9 Hz, 1H), 8.01 2977, 2939, C₂₁H₂₆FN₂O₆, (d, J = 5.2 Hz, 1H), 7.13-7.06 (m, 1733, 1649, 421.1769; found, 1H), 6.88 (d, J = 5.3 Hz, 1H), 6.62- 1528, 1450, 421.1770 6.54 (m, 2H), 5.21-5.12 (m, 1H), 1278, 1262, 4.73-4.63 (m, 1H), 3.95 (s, 3H), 3.79 (s, 1149, 952 3H), 3.42-3.32 (m, 1H), 1.51 (d, J = cm⁻¹ 7.2 Hz, 3H), 1.24 (d, J = 7.0 Hz, 3H), 1.14 (d, J = 6.3 Hz, 3H). ¹⁹FNMR(471 MHz, CDCl₃) δ −113.8-−113.9 (m). 174 ESIMS m/z 387.3 ¹H NMR (400 MHz, CDCl₃) δ 12.16 [(M + H)+] (d, J = 4.9 Hz, 1H), 8.50 (d, J = 7.8 Hz, 1H), 8.01 (dd, J = 5.2, 2.7 Hz, 1H), 7.21-7.01 (m, 4H), 6.88 (dd, J = 5.3, 1.9 Hz, 1H), 5.18 (dq, J = 8.3, 6.3 Hz, 1H), 4.73 (p, J = 7.3 Hz, 1H), 3.95 (d, J = 1.6 Hz, 3H), 3.19 (dq, J = 9.0, 6.9 Hz, 1H), 2.35 (s, 3H), 1.55 (d, J = 7.0 Hz, 3H), 1.26 (dd, J = 6.9, 3.8 Hz, 3H), 1.13 (dd, J = 9.0, 6.2 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 171.85, 168.74, 155.41, 148.80, 141.65, 140.49, 135.53, 130.54, 126.37, 126.31, 126.29, 109.46, 56.07, 53.40, 48.00, 39.74, 19.94, 18.28, 18.27, 17.52, −0.01. 175 ¹H NMR (400 MHz, CDCl₃) δ 12.16 (d, J = 0.6 Hz, 1H), 8.51 (d, J = 7.9 Hz, 1H), 8.00 (d, J = 5.2 Hz, 1H), 7.22- 7.02 (m, 5H), 6.88 (d, J = 5.2 Hz, 1H), 5.16 (dq, J = 8.3, 6.2 Hz, 1H), 4.78- 4.65 (m, 1H), 3.95 (s, 3H), 3.20 (dq, J = 8.3, 6.9 Hz, 1H), 2.35 (s, 3H), 1.56 (d, J = 7.2 Hz, 3H), 1.26 (d, J = 6.9 Hz, 3H), 1.15 (d, J = 6.3 Hz, 3H). 176 ESIMS m/z 416 ¹H NMR (300 MHz, CDCl₃) δ 12.18 ([M + H]⁺) (s, 1H), 8.52 (d, J = 7.9 Hz, 1H), 8.00 (d, J = 5.2 Hz, 1H), 7.13-7.01 (m, 2H), 6.88 (d, J = 5.2 Hz, 1H), 6.67 (d, J = 8.5 Hz, 2H), 5.12-4.98 (m, 1H), 4.72 (p, J = 7.3 Hz, 1H), 3.95 (s, 3H), 2.92 (s, 6H), 2.88-2.75 (m, 1H), 1.57 (s, 3H), 1.26 (dd, J = 7.1, 4.0 Hz, 3H), 1.11 (d, J = 6.2 Hz, 3H). ¹³C NMR (75 MHz, CDCl₃) δ 148.75, 140.49, 130.54, 128.42, 112.68, 109.42, 40.70, 18.33 (d, J = 22.8 Hz), 0.01. 177 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.57 (s, [M + H]⁺ calcd for 1H), 8.34 (d, J = 5.4 Hz, 1H), 7.07 (d, C₂₄H₃₀N₂O₆, J = 8.6 Hz, 1H), 7.01 (d, J = 5.5 Hz, 1H), 443.2177; found, 6.97 (d, J = 6.7 Hz, 2H), 5.12 (dq, J = 443.2170 8.5, 6.3 Hz, 1H), 4.78-4.67 (m, 1H), 3.91 (s, 3H), 3.19-3.09 (m, 1H), 2.41 (s, 3H), 2.31 (s, 3H), 2.28 (s, 3H), 1.52 (d, J = 7.2 Hz, 3H), 1.23 (d, J = 6.9 Hz, 3H), 1.11 (d, J = 6.2 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 172.41, 168.96, 162.36, 159.42, 146.70, 141.53, 138.75, 137.46, 135.67, 135.33, 131.26, 126.95, 126.26, 109.75, 76.48, 56.29, 48.16, 39.45, 20.89, 20.78, 19.90, 18.76, 18.48, 17.67. 178 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.57 (s, [M + H]⁺ calcd for 1H), 8.35 (d, J = 5.5 Hz, 1H), 7.07 (d, C₂₄H₃₀N₂O₆, J = 7.7 Hz, 1H), 7.01 (d, J = 5.5 Hz, 1H), 443.2177; found, 6.98 (d, J = 7.4 Hz, 2H), 5.12 (dq, J = 443.2172 8.5, 6.2 Hz, 1H), 4.72 (p, J = 7.2 Hz, 1H), 3.91 (s, 3H), 3.18-3.09 (m, 1H), 2.41 (s, 3H), 2.31 (s, 3H), 2.27 (s, 3H), 1.50 (d, J = 7.2 Hz, 3H), 1.22 (d, J = 6.9 Hz, 3H), 1.10 (d, J = 6.2 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 172.41, 168.97, 162.40, 159.43, 146.70, 141.52, 138.72, 137.46, 135.64, 135.37, 131.24, 126.98, 126.27, 109.75, 76.37, 56.29, 48.04, 39.38, 20.88, 20.78, 19.92, 18.59, 18.24, 17.73. 179 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.51 (s, [M + H]⁺ calcd for 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.09- C₂₆H₃₄N₂O₆, 7.04 (m, 1H), 7.02-6.94 (m, 3H), 5.11 471.2490; found, (dq, J = 8.5, 6.2 Hz, 1H), 4.73 (p, J = 471.2484 7.2 Hz, 1H), 3.89 (s, 3H), 3.19-3.09 (m, 1H), 2.96 (p, J = 7.0 Hz, 1H), 2.31 (s, 3H), 2.28 (s, 3H), 1.51 (d, J = 7.2 Hz, 3H), 1.36 (dd, J = 7.0, 1.4 Hz, 5H), 1.23 (d, J = 6.9 Hz, 3H), 1.11 (d, J = 6.2 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.73, 172.50, 162.34, 159.40, 146.59, 141.90, 138.78, 137.63, 135.66, 135.33, 131.25, 126.95, 126.28, 109.58, 76.41, 56.29, 48.13, 39.45, 33.94, 20.89, 19.90, 18.80, 18.48, 17.66. 180 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.50 (s, [M + H]⁺ calcd for 1H), 8.34 (d, J = 5.4 Hz, 1H), 7.07 (d, C₂₆H₃₄N₂O₆, J = 7.8 Hz, 1H), 7.03-6.93 (m, 3H), 471.2490; found, 5.12 (dq, J = 8.5, 6.2 Hz, 1H), 4.72 (p, 471.2490 J = 7.1 Hz, 1H), 3.89 (s, 3H), 3.20- 3.09 (m, 1H), 2.96 (p, J = 7.0 Hz, 1H), 2.31 (s, 3H), 2.27 (s, 3H), 1.49 (d, J = 7.1 Hz, 3H), 1.37 (dd, J = 6.9, 2.0 Hz, 6H), 1.22 (d, J = 6.9 Hz, 3H), 1.09 (d, J = 6.2 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.74, 172.50, 162.39, 159.41, 146.59, 141.90, 138.76, 137.63, 135.63, 135.37, 131.23, 126.98, 126.28, 109.58, 76.29, 56.29, 48.03, 39.40, 33.94, 20.88, 19.91, 18.81, 18.59, 18.25, 17.74. 181 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.37 (s, [M + H]⁺ calcd for 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.17 (dd, C₂₃H₂₇FN₂O₆, J = 8.4, 5.9 Hz, 1H), 7.01 (d, J = 5.4 447.1926; found, Hz, 1H), 6.84-6.75 (m, 2H), 5.10 (p, 447.1923 J = 6.4 Hz, 1H), 4.57 (p, J = 7.2 Hz, 1H), 3.91 (s, 3H), 3.22 (p, J = 7.0 Hz, 1H), 2.40 (s, 2H), 2.33 (s, 3H), 1.34 (d, J = 7.1 Hz, 2H), 1.27-1.18 (m, 6H). ¹³C NMR (126 MHz, CDCl₃) δ 171.87, 168.95, 162.24, 161.89, 159.95, 159.44, 146.62, 141.38, 138.44, 137.47, 136.77, 127.73, 116.74, 116.58, 112.79, 112.62, 109.75, 75.32, 56.29, 47.87, 38.50, 20.76, 19.89, 18.40, 17.06, 16.72. 182 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.53 (s, [M + H]⁺ calcd for 1H), 8.35 (d, J = 5.5 Hz, 1H), 7.22- C₂₂H₂₅FN₂O₆, 7.13 (m, 2H), 7.05-6.93 (m, 3H), 5.05 433.1769; found, (h, J = 6.5 Hz, 1H), 4.71 (ddt, J = 14.7, 433.1767 10.3, 5.3 Hz, 1H), 3.91 (s, 3H), 2.91 (p, J = 6.8 Hz, 1H), 2.41 (s, 3H), 1.48 (d, J = 7.2 Hz, 3H), 1.27 (d, J = 7.2 Hz, 3H), 1.08 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 170.34, 167.06, 160.68, 160.54, 158.74, 157.59, 144.78, 139.51, 136.64, 136.61, 135.58, 127.40, 127.34, 113.37, 113.21, 107.93, 73.96, 54.42, 46.14, 42.14, 18.85, 16.52, 15.76, 15.38. 183 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.56 (s, [M + H]⁺ calcd for 1H), 8.35 (d, J = 5.4 Hz, 1H), 7.09 (d, C₂₄H₃₀N₂O₇, J = 8.4 Hz, 1H), 7.02 (d, J = 5.5 Hz, 1H), 459.2126; found, 6.75-6.66 (m, 2H), 5.15-5.05 (m, 459.2096 1H), 4.72 (pd, J = 7.3, 1.5 Hz, 1H), 3.92 (s, 3H), 3.76 (s, 3H), 3.16-3.07 (m, 1H), 2.41 (s, 3H), 2.32 (s, 3H), 1.50 (d, J = 7.2 Hz, 3H), 1.22 (d, J = 6.8 Hz, 3H), 1.10 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 170.45, 167.03, 160.47, 157.55, 155.65, 144.76, 139.57, 135.54, 135.02, 132.00, 125.43, 113.97, 109.50, 107.85, 74.52, 54.38, 53.17, 46.15, 37.09, 18.83, 18.29, 16.63, 16.24, 15.80. 184 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.52 (s, [M + H]⁺ calcd for 1H), 8.36 (d, J = 5.5 Hz, 1H), 7.11 C₂₅H₃₁FN₂O₆, (ddd, J = 7.5, 5.9, 1.5 Hz, 1H), 7.02 (d, 475.2239; found, J = 5.5 Hz, 1H), 6.83 (t, J = 8.1 Hz, 475.2238 2H), 5.06 (dq, J = 8.1, 6.3 Hz, 1H), 4.66 (dd, J = 9.4, 4.7 Hz, 1H), 3.92 (s, 3H), 3.20-3.08 (m, 1H), 2.40 (s, 3H), 2.32 (d, J = 2.3 Hz, 3H), 2.29 (td, J = 6.9, 4.8 Hz, 1H), 1.23 (d, J = 6.9 Hz, 3H), 1.11 (d, J = 6.2 Hz, 3H), 1.01 (d, J = 6.8 Hz, 3H), 0.93 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.24, 168.92, 162.74, 161.89, 159.95, 159.47, 146.68, 141.59, 137.81, 137.76, 137.49, 127.86, 127.79, 117.00, 116.83, 113.00, 112.83, 109.75, 76.14, 57.17, 56.31, 39.04, 31.46, 20.79, 20.00, 19.38, 18.45, 17.47, 17.44. 185 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.41 (s, [M + H]⁺ calcd for 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.16 (dd, C₂₅H₃₁FN₂O₆, J = 9.0, 5.9 Hz, 1H), 7.01 (d, J = 5.4 475.2239; found, Hz, 1H), 6.81 (t, J = 8.0 Hz, 2H), 5.15- 475.2236 5.07 (m, 1H), 4.53 (dd, J = 9.5, 4.5 Hz, 1H), 3.90 (s, 3H), 3.24-3.16 (m, 1H), 2.38 (s, 3H), 2.34 (s, 3H), 1.88 (td, J = 6.9, 4.5 Hz, 1H), 1.26 (d, J = 6.2 Hz, 3H), 1.21 (d, J = 6.9 Hz, 3H), 0.81 (d, J = 6.8 Hz, 3H), 0.63 (d, J = 6.8 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 169.14, 167.00, 160.78, 160.02, 158.08, 157.53, 144.77, 139.62, 136.49, 135.51, 135.45, 125.64, 125.57, 114.82, 114.66, 110.95, 110.79, 107.84, 73.69, 54.92, 54.40, 36.84, 29.39, 18.86, 17.99, 17.09, 15.75, 15.30, 15.12. 186 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.43 (s, [M + H]⁺ calcd for 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.24- C₂₅H₃₂N₂O₆, 7.19 (m, 1H), 7.09 (dddd, J = 29.3, 457.2333; found, 14.6, 7.2, 2.9 Hz, 3H), 7.00 (d, J = 5.5 457.2330 Hz, 1H), 5.14 (dq, J = 8.2, 6.2 Hz, 1H), 4.53 (dd, J = 9.4, 4.3 Hz, 1H), 3.90 (s, 3H), 3.26 (q, J = 7.4 Hz, 1H), 2.38 (s, 3H), 2.36 (s, 3H), 1.91-1.78 (m, 1H), 1.27 (d, J = 6.2 Hz, 3H), 1.25-1.20 (m, 3H), 0.78 (d, J = 6.9 Hz, 3H), 0.58 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 169.16, 166.97, 160.75, 157.48, 144.73, 139.69, 135.46, 134.11, 128.31, 124.26, 124.06, 107.75, 73.76, 54.85, 54.36, 37.31, 29.36, 18.84, 17.91, 17.07, 15.67, 15.06, 15.00. 187 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.50 (d, [M + H]⁺ calcd for J = 9.8 Hz, 1H), 8.35 (d, J = 5.4 Hz, C₂₄H₂₉FN₂O₆, 1H), 7.14 (dd, J = 8.6, 5.5 Hz, 2H), 461.2082; found, 7.03 (d, J = 5.5 Hz, 1H), 6.94 (t, J = 461.2082 8.7 Hz, 2H), 5.07-4.99 (m, 1H), 4.65 (dd, J = 9.4, 4.7 Hz, 1H), 3.92 (s, 3H), 2.93-2.86 (m, 1H), 2.40 (s, 3H), 2.26 (pd, J = 6.8, 4.7 Hz, 1H), 1.28 (d, J = 7.0 Hz, 3H), 1.10 (d, J = 6.3 Hz, 3H), 0.99 (d, J = 6.9 Hz, 3H), 0.92 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 169.14, 167.00, 160.80, 160.63, 158.69, 157.57, 144.75, 139.63, 136.70, 136.67, 135.57, 127.33, 127.27, 113.31, 113.14, 107.86, 74.15, 55.24, 54.40, 42.02, 29.52, 18.86, 17.37, 16.09, 15.54, 15.21. 188 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.53 (d, [M + H]⁺ calcd for J = 9.3 Hz, 1H), 8.36 (d, J = 5.5 Hz, C₂₆H₃₄N₂O₇, 1H), 7.07 (d, J = 9.5 Hz, 1H), 7.02 (d, J = 487.2439; found, 5.5 Hz, 1H), 6.72-6.66 (m, 2H), 487.2427 5.06 (dq, J = 8.5, 6.3 Hz, 1H), 4.67 (dd, J = 9.4, 4.6 Hz, 1H), 3.91 (s, 3H), 3.76 (s, 3H), 3.15-3.06 (m, 1H), 2.40 (s, 3H), 2.31 (m, 4H), 1.23 (d, J = 6.9 Hz, 3H), 1.10 (d, J = 6.2 Hz, 3H), 1.02 (d, J = 6.8 Hz, 3H), 0.94 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 169.38, 167.00, 160.80, 157.51, 155.65, 144.76, 139.71, 135.53, 134.94, 132.15, 125.41, 109.49, 107.80, 74.70, 55.25, 54.37, 53.18, 37.08, 29.56, 18.86, 18.27, 17.47, 16.60, 15.86, 15.53. 189 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.61- [M + H]⁺ calcd for 8.47 (m, 1H), 8.36 (d, J = 5.4 Hz, 1H), C₂₅H₃₁FN₂O₆, 7.13 (dd, J = 9.6, 5.7 Hz, 1H), 7.02 (d, 475.2239; found, J = 5.5 Hz, 1H), 6.88-6.79 (m, 2H), 475.2238 5.09 (dq, J = 8.0, 6.3 Hz, 1H), 4.64 (dd, J = 9.1, 5.0 Hz, 1H), 3.92 (s, 3H), 3.13 (p, J = 7.1 Hz, 1H), 2.41 (s, 3H), 2.33 (s, 3H), 2.29 (qd, J = 7.0, 5.2 Hz, 1H), 1.23 (d, J = 7.0 Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H), 0.99 (d, J = 6.8 Hz, 3H), 0.96 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 169.44, 167.00, 160.79, 159.96, 158.02, 157.53, 144.78, 139.68, 135.91, 135.53, 135.50, 125.99, 125.93, 115.05, 114.89, 111.11, 110.95, 107.83, 73.93, 55.11, 54.38, 37.14, 29.57, 18.86, 18.10, 17.03, 16.32, 16.00, 15.50. 190 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.40 (s, [M + H]⁺ calcd for 1H), 8.34 (d, J = 5.4 Hz, 1H), 7.18 (dd, C₂₅H₃₁FN₂O₆, J = 9.5, 5.8 Hz, 1H), 7.02 (d, J = 5.5 475.2239; found, Hz, 1H), 6.84-6.75 (m, 2H), 5.10 (p, 475.2235 J = 6.4 Hz, 1H), 4.51 (dd, J = 9.2, 5.1 Hz, 1H), 3.92 (s, 3H), 3.22 (p, J = 7.1 Hz, 1H), 2.40 (s, 3H), 2.33 (s, 3H), 2.15 (pd, J = 6.9, 5.0 Hz, 1H), 1.23 (d, J = 7.1 Hz, 3H), 1.21 (d, J = 6.3 Hz, 3H), 0.88 (d, J = 6.9 Hz, 3H), 0.84 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 170.81, 168.93, 162.52, 161.93, 159.99, 159.45, 146.63, 141.52, 138.48, 138.42, 137.46, 136.82, 136.79, 127.88, 127.82, 116.75, 116.59, 112.77, 112.61, 109.71, 75.30, 57.02, 56.30, 38.43, 31.44, 20.78, 19.90, 18.78, 17.72, 17.08, 16.67. 191 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.42 (s, [M + H]⁺ calcd for 1H), 8.35 (d, J = 5.4 Hz, 1H), 7.23 (dd, C₂₅H₃₂N₂O₆, J = 7.8, 1.4 Hz, 1H), 7.15-7.03 (m, 457.2333; found, 3H), 7.02 (d, J = 5.4 Hz, 1H), 5.13 (p, 457.2331 J = 6.4 Hz, 1H), 4.53 (dd, J = 9.2, 4.9 Hz, 1H), 3.91 (s, 3H), 3.28 (p, J = 7.1 Hz, 1H), 2.40 (s, 3H), 2.36 (s, 3H), 2.14 (pd, J = 6.9, 4.9 Hz, 1H), 1.26 (d, J = 7.2 Hz, 3H), 1.22 (d, J = 6.3 Hz, 3H), 0.86 (d, J = 6.9 Hz, 3H), 0.81 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 170.77, 168.93, 162.52, 159.43, 146.63, 141.61, 141.09, 137.44, 136.15, 130.25, 126.37, 126.20, 126.09, 109.69, 75.37, 57.02, 56.29, 38.88, 31.51, 20.79, 19.83, 18.77, 17.70, 16.91, 16.26. 192 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.58- [M + H]⁺ calcd for 8.45 (m, 1H), 8.36 (d, J = 5.5 Hz, 1H), C₂₄H₂₉FN₂O₆, 7.16 (ddd, J = 10.8, 6.6, 3.7 Hz, 2H), 457.2333; found, 7.02 (d, J = 5.5 Hz, 1H), 7.01-6.94 457.2331 (m, 2H), 5.10-4.99 (m, 1H), 4.63 (dd, J = 9.2, 5.0 Hz, 1H), 3.92 (s, 3H), 2.90 (p, J = 7.1 Hz, 1H), 2.40 (d, J = 2.1 Hz, 3H), 2.31-2.21 (m, 1H), 1.28 (d, J = 7.0 Hz, 3H), 1.09 (d, J = 6.4 Hz, 3H), 1.00-0.97 (m, 3H), 0.96 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.25, 168.93, 162.72, 162.58, 160.64, 159.46, 146.69, 141.58, 138.61, 138.59, 137.46, 129.30, 129.23, 115.28, 115.11, 109.76, 75.84, 57.06, 56.31, 44.06, 31.47, 20.79, 18.93, 17.96, 17.84, 17.26. 193 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.62- [M + H]⁺ calcd for 8.50 (m, 1H), 8.36 (d, J = 5.4 Hz, 1H), C₂₆H₃₄N₂O₇, 7.10 (d, J = 8.4 Hz, 1H), 7.02 (d, J = 487.2439; found, 5.5 Hz, 1H), 6.75-6.67 (m, 2H), 5.09 487.2434 (dq, J = 8.4, 6.3 Hz, 1H), 4.65 (dd, J = 9.1, 4.9 Hz, 1H), 3.91 (s, 3H), 3.75 (s, 3H), 3.17-3.06 (m, 1H), 2.40 (s, 3H), 2.32 (m, 4H), 1.22 (d, J = 6.9 Hz, 3H), 1.11 (d, J = 6.2 Hz, 3H), 0.99 (d, J = 6.8 Hz, 3H), 0.97 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 169.50, 167.02, 160.80, 157.52, 155.67, 144.82, 139.74, 135.53, 135.01, 132.08, 125.49, 114.01, 109.51, 107.84, 74.46, 55.12, 54.40, 53.18, 37.11, 29.65, 18.89, 18.31, 17.06, 16.41, 16.02, 15.83. 194 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.45- [M + H]⁺ calcd for 8.36 (m, 1H), 8.33 (d, J = 5.5 Hz, 1H), C₂₃H₂₈N₂O₆, 7.25-7.17 (m, 1H), 7.17-7.03 (m, 429.2020; found, 3H), 7.01 (d, J = 5.5 Hz, 1H), 5.18- 429.2021 5.09 (m, 1H), 4.61-4.48 (m, 1H), 3.91 (s, 3H), 3.28 (p, J = 7.3 Hz, 1H), 2.39 (d, J = 5.8 Hz, 3H), 2.36 (s, 3H), 1.32 (d, J = 7.2 Hz, 3H), 1.26 (d, J = 7.0 Hz, 3H), 1.23 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 169.93, 167.04, 160.36, 157.55, 144.72, 139.53, 139.14, 135.53, 134.21, 128.32, 124.37, 124.31, 107.85, 73.52, 54.40, 46.07, 37.09, 18.84, 17.93, 16.51, 15.05, 14.45. 195 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.54 (d, [M + H]⁺ calcd for J = 7.4 Hz, 1H), 8.34 (d, J = 5.4 Hz, C₂₃H₂₇FN₂O₆, 1H), 7.13 (dd, J = 9.5, 5.8 Hz, 1H), 447.1926; found, 7.02 (d, J = 5.5 Hz, 1H), 6.88-6.81 447.1922 (m, 2H), 5.09 (dq, J = 8.2, 6.3 Hz, 1H), 4.72 (p, J = 7.3 Hz, 1H), 3.91 (s, 3H), 3.20-3.09 (m, 1H), 2.41 (s, 3H), 2.33 (s, 3H), 1.50 (d, J = 7.1 Hz, 3H), 1.23 (d, J = 6.8 Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 170.39, 167.02, 160.44, 159.98, 158.04, 157.54, 144.76, 139.53, 135.94, 135.88, 135.55, 135.49, 125.94, 125.88, 115.11, 114.94, 111.06, 110.90, 107.87, 74.14, 54.38, 46.21, 37.21, 18.84, 18.08, 16.77, 16.43, 15.46. 196 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.44 (s, [M + H]⁺ calcd for 1H), 8.34 (d, J = 5.4 Hz, 1H), 7.12 C₂₄H₂₉FN₂O₆, (ddd, J = 9.3, 4.5, 2.0 Hz, 1H), 7.00 (d, 461.2082; found, J = 5.5 Hz, 1H), 6.86 (dd, J = 9.0, 6.7 461.2082 Hz, 2H), 5.12 (dq, J = 7.9, 6.3 Hz, 1H), 4.18 (dd, J = 5.7, 2.8 Hz, 2H), 3.90 (s, 3H), 3.14 (p, J = 7.1 Hz, 1H), 2.95 (p, J = 7.0 Hz, 1H), 2.32 (s, 3H), 1.37 (d, J = 7.0 Hz, 6H), 1.22 (d, J = 7.0 Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.71, 169.37, 163.02, 161.95, 160.00, 159.48, 146.62, 141.68, 137.91, 137.73, 137.35, 137.32, 127.89, 127.82, 117.05, 116.89, 113.04, 112.87, 109.72, 76.09, 56.31, 41.38, 39.11, 33.98, 20.01, 18.81, 18.22, 17.42. 197 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.34 (d, [M + H]⁺ calcd for J = 5.0 Hz, 1H), 8.32 (d, J = 5.4 Hz, C₂₄H₂₉FN₂O₆, 1H), 7.21-7.10 (m, 1H), 6.99 (d, J = 461.2082; found, 5.4 Hz, 1H), 6.84-6.76 (m, 2H), 5.13 461.2082 (p, J = 6.4 Hz, 1H), 4.17-3.92 (m, 2H), 3.90-3.88 (s, 3H), 3.22 (p, J = 7.1 Hz, 1H), 2.94 (p, J = 7.0 Hz, 1H), 2.33 (s, 3H), 1.36 (d, J = 7.0 Hz, 6H), 1.23 (dd, J = 6.7, 1.3 Hz, 6H). ¹³C NMR (126 MHz, CDCl₃) δ 174.69, 169.03, 162.91, 161.95, 160.01, 159.46, 146.58, 141.61, 138.48, 137.71, 136.72, 136.69, 127.84, 127.77, 116.78, 116.62, 112.83, 112.67, 109.70, 75.49, 56.30, 41.22, 38.58, 33.96, 19.87, 19.86, 18.80, 17.11, 16.56. 198 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.33 (m, [M + H]⁺ calcd for 2H), 7.21 (dd, J = 7.6, 1.5 Hz, 1H), C₂₄H₃₀N₂O₆, 7.10 (ttd, J = 14.3, 7.8, 7.3, 1.8 Hz, 443.2177; found, 3H), 6.98 (d, J = 5.5 Hz, 1H), 5.17 (h, 443.2174 J = 6.5 Hz, 1H), 4.14-3.90 (m, 2H), 3.89 (s, 3H), 3.33-3.23 (m, 1H), 2.94 (p, J = 7.0 Hz, 1H), 2.35 (s, 3H), 1.36 (d, J = 7.0 Hz, 6H), 1.28-1.19 (m, 6H). ¹³C NMR (126 MHz, CDCl₃) δ 174.69, 169.05, 162.90, 159.44, 146.58, 141.67, 141.02, 137.68, 136.17, 130.25, 126.30, 126.27, 126.11, 109.66, 75.58, 56.29, 41.22, 39.10, 33.97, 19.80, 18.80, 18.75, 17.05, 16.24. 199 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.44 (t, [M + H]⁺ calcd for J = 5.5 Hz, 1H), 8.33 (d, J = 5.4 Hz, C₂₃H₂₇FN₂O₆, 1H), 7.18-7.11 (m, 2H), 7.02-6.92 447.1926; found, (m, 3H), 5.14-5.02 (m, 1H), 4.22- 447.1926 4.13 (m, 2H), 3.90 (s, 3H), 3.02-2.84 (m, 2H), 1.37 (d, J = 7.0 Hz, 6H), 1.30- 1.23 (m, 3H), 1.09 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.71, 169.27, 163.03, 162.63, 160.69, 159.48, 146.62, 141.66, 138.52, 137.74, 129.30, 129.23, 115.31, 115.14, 109.73, 76.02, 56.31, 44.12, 41.41, 33.98, 18.81, 17.81, 17.26. 200 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.45 (t, [M + H]⁺ calcd for J = 5.4 Hz, 1H), 8.33 (d, J = 5.4 Hz, C₂₅H₃₂N₂O₇, 1H), 7.08 (d, J = 8.4 Hz, 1H), 7.00 (d, 473.2282; found, J = 5.5 Hz, 1H), 6.77-6.67 (m, 2H), 473.2275 5.12 (dq, J = 8.1, 6.2 Hz, 1H), 4.25- 4.14 (m, 2H), 3.89 (s, 3H), 3.77 (s, 3H), 3.16-3.05 (m, 1H), 2.96 (p, J = 7.0 Hz, 1H), 2.31 (s, 3H), 1.37 (d, J = 7.0 Hz, 6H), 1.22 (d, J = 7.0 Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.71, 169.43, 163.02, 159.46, 157.66, 146.63, 141.71, 137.71, 136.96, 133.86, 127.39, 115.94, 111.46, 109.70, 76.54, 56.30, 55.11, 41.41, 39.04, 33.98, 20.18, 18.81, 18.27, 17.62. 201 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.36 (s, [M + H]⁺ calcd for 1H), 8.31 (d, J = 5.4 Hz, 1H), 7.16 C₂₅H₃₁FN₂O₆, (ddd, J = 13.0, 8.8, 6.0 Hz, 1H), 6.97 475.2239; found, (d, J = 5.4 Hz, 1H), 6.81 (t, J = 7.8 Hz, 475.2234 2H), 5.11 (dq, J = 8.3, 6.4 Hz, 1H), 4.56 (p, J = 7.3 Hz, 1H), 3.88 (s, 3H), 3.26-3.16 (m, 1H), 2.99-2.90 (m, 1H), 2.34 (s, 3H), 1.35 (d, J = 6.9 Hz, 6H), 1.27 (d, J = 6.3 Hz, 3H), 1.21 (d, J = 7.1 Hz, 3H), 1.08 (d, J = 7.1 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.68, 172.20, 162.29, 161.91, 159.97, 159.42, 146.55, 141.88, 138.36, 138.30, 137.64, 137.22, 137.19, 127.57, 127.50, 116.70, 116.54, 112.85, 112.68, 109.58, 75.44, 56.28, 47.83, 38.90, 33.93, 19.91, 18.80, 18.20, 17.70, 17.22. 202 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.35 [M + H]⁺ calcd for (dd, J = 8.2, 5.5 Hz, 1H), 8.31 (d, J = C₂₅H₃₂N₂O₆, 5.4 Hz, 1H), 7.19 (dd, J = 7.7, 1.4 Hz, 457.2333; found, 1H), 7.09 (ttd, J = 14.5, 7.2, 1.7 Hz, 457.2331 3H), 6.97 (d, J = 5.4 Hz, 1H), 5.15 (dq, J = 7.7, 6.1 Hz, 1H), 4.60-4.45 (m, 1H), 3.88 (s, 3H), 3.26 (dp, J = 14.7, 7.2 Hz, 1H), 2.93 (p, J = 7.1 Hz, 1H), 2.36 (s, 3H), 1.35 (d, J = 7.0 Hz, 6H), 1.28 (d, J = 6.3 Hz, 3H), 1.24 (d, J = 7.2 Hz, 3H), 1.01 (d, J = 7.2 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.68, 172.25, 162.27, 159.39, 146.55, 141.96, 141.54, 137.60, 136.03, 130.21, 126.16, 125.98, 109.53, 77.28, 75.56, 56.27, 47.84, 39.44, 33.93, 19.84, 18.81, 18.14, 17.71, 17.01. 203 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.46 (s, [M + H]⁺ calcd for 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.15 (dd, C₂₄H₂₉FN₂O₆, J = 8.6, 5.5 Hz, 2H), 7.01-6.92 (m, 461.2082; found, 3H), 5.09-5.00 (m, 1H), 4.71 (p, J = 461.2082 7.3 Hz, 1H), 3.89 (s, 3H), 3.00-2.86 (m, 2H), 1.47 (d, J = 7.1 Hz, 3H), 1.36 (dd, J = 7.0, 1.3 Hz, 6H), 1.27 (d, J = 7.0 Hz, 3H), 1.09 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.71, 172.30, 162.61, 162.36, 160.67, 159.46, 146.57, 141.90, 138.63, 137.71, 129.29, 129.23, 115.27, 115.10, 109.62, 75.96, 56.30, 48.10, 44.13, 33.96, 18.81, 18.72, 17.93, 17.20. 204 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.50 (d, [M + H]⁺ calcd for J = 9.7 Hz, 1H), 8.33 (d, J = 5.4 Hz, C₂₆H₃₄N₂O₇, 1H), 7.09 (d, J = 8.3 Hz, 1H), 6.99 (d, 487.2439; found, J = 5.5 Hz, 1H), 6.76-6.66 (m, 2H), 487.2431 5.08 (dq, J = 8.3, 6.2 Hz, 1H), 4.73 (p, J = 7.3 Hz, 1H), 3.89 (s, 3H), 3.77 (s, 3H), 3.18-3.05 (m, 1H), 2.95 (p, J = 7.0 Hz, 1H), 2.32 (s, 3H), 1.50 (d, J = 7.2 Hz, 3H), 1.36 (dd, J = 7.0, 1.5 Hz, 6H), 1.22 (d, J = 6.8 Hz, 3H), 1.11 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.70, 172.48, 162.36, 159.43, 157.65, 146.58, 141.96, 137.67, 136.91, 134.03, 127.40, 115.92, 111.45, 109.59, 76.46, 56.29, 55.12, 48.15, 39.14, 33.95, 20.19, 18.81, 18.43, 17.63. 205 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.51- [M + H]⁺ calcd for 8.39 (m, 1H), 8.34 (d, J = 5.3 Hz, 1H), C₂₅H₃₁FN₂O₆, 7.13 (dd, J = 9.4, 5.8 Hz, 1H), 6.99 (d, 475.2239; found, J = 5.4 Hz, 1H), 6.87-6.81 (m, 2H), 475.2239 5.09 (dq, J = 7.9, 6.2 Hz, 1H), 4.71 (p, J = 7.3 Hz, 1H), 3.89 (s, 3H), 3.13 (p, J = 7.1 Hz, 1H), 2.95 (p, J = 7.0 Hz, 1H), 2.33 (s, 3H), 1.48 (d, J = 7.1 Hz, 3H), 1.39-1.33 (m, 6H), 1.22 (d, J = 6.9 Hz, 3H), 1.10 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.71, 172.43, 162.41, 161.91, 159.97, 159.46, 146.57, 141.90, 137.88, 137.82, 137.47, 127.91, 127.85, 117.01, 116.84, 113.03, 112.87, 109.63, 75.88, 56.30, 48.01, 39.13, 33.96, 20.02, 18.81, 18.50, 18.12, 17.48. 206 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.35- [M + H]⁺ calcd for 8.27 (m, 2H), 7.22 (dd, J = 7.7, 1.4 Hz, C₂₅H₃₂N₂O₆, 1H), 7.17-7.03 (m, 3H), 6.98 (d, J = 457.2333; found, 5.4 Hz, 1H), 5.14 (p, J = 6.5 Hz, 1H), 457.2332 4.56 (p, J = 7.2 Hz, 1H), 3.89 (s, 3H), 3.28 (p, J = 7.0 Hz, 1H), 2.94 (p, J = 7.0 Hz, 1H), 2.35 (s, 3H), 1.39-1.34 (m, 6H), 1.31 (d, J = 7.2 Hz, 3H), 1.25 (d, J = 7.1 Hz, 3H), 1.22 (d, J = 6.4 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.70, 171.97, 162.25, 159.43, 146.50, 141.92, 141.08, 137.66, 136.14, 130.23, 126.33, 126.21, 126.09, 109.55, 75.33, 56.29, 47.95, 39.03, 33.95, 19.82, 18.81, 18.47, 16.96, 16.35. 207 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.45 (s, [M + H]⁺ calcd for 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.20- C₂₄H₂₉FN₂O₆, 7.12 (m, 2H), 7.02-6.94 (m, 3H), 5.10- 461.2082; found, 4.99 (m, 1H), 4.70 (p, J = 7.3 Hz, 461.2082 1H), 3.89 (s, 3H), 2.94 (ddt, J = 15.3, 14.2, 7.1 Hz, 2H), 1.47 (d, J = 7.1 Hz, 3H), 1.38-1.34 (m, 6H), 1.27 (d, J = 6.9 Hz, 3H), 1.07 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.72, 172.36, 162.62, 162.44, 160.67, 159.46, 146.57, 141.88, 138.58, 137.70, 129.33, 129.26, 115.28, 115.11, 109.63, 75.77, 56.30, 48.03, 44.07, 33.96, 18.81, 18.46, 17.65, 17.30. 208 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.49 (d, [M + H]⁺ calcd for J = 5.7 Hz, 1H), 8.34 (d, J = 5.5 Hz, C₂₆H₃₄N₂O₇, 1H), 7.09 (d, J = 8.3 Hz, 1H), 6.99 (d, 487.2439; found, J = 5.4 Hz, 1H), 6.75-6.67 (m, 2H), 487.2432 5.09 (dq, J = 8.2, 6.2 Hz, 1H), 4.72 (p, J = 7.2 Hz, 1H), 3.89 (s, 3H), 3.76 (s, 3H), 3.15-3.05 (m, 1H), 2.96 (p, J = 7.0 Hz, 1H), 2.32 (s, 3H), 1.49 (d, J = 7.2 Hz, 3H), 1.39-1.34 (m, 6H), 1.21 (d, J = 6.9 Hz, 3H), 1.09 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.71, 172.49, 162.41, 159.44, 157.62, 146.58, 141.96, 137.67, 136.95, 134.00, 127.40, 115.94, 111.45, 109.60, 76.36, 56.29, 55.10, 48.06, 39.08, 33.96, 20.21, 18.82, 18.58, 18.19, 17.74. 209 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.44 (d, [M + H]⁺ calcd for J = 9.0 Hz, 1H), 8.34 (d, J = 5.4 Hz, C₂₇H₃₅FN₂O₆, 1H), 7.16-7.08 (m, 1H), 6.99 (d, J = 503.2552; found, 5.5 Hz, 1H), 6.82 (t, J = 7.9 Hz, 2H), 503.2547 5.06 (dq, J = 8.0, 6.2 Hz, 1H), 4.66 (dd, J = 9.4, 4.8 Hz, 1H), 3.89 (s, 3H), 3.20- 3.09 (m, 1H), 2.95 (p, J = 7.0 Hz, 1H), 2.32 (s, 3H), 2.28 (qd, J = 7.0, 4.9 Hz, 1H), 1.39-1.32 (m, 6H), 1.23 (d, J = 6.9 Hz, 3H), 1.11 (d, J = 6.2 Hz, 3H), 1.01 (d, J = 6.8 Hz, 3H), 0.92 (d, J = 6.8 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.67, 171.34, 162.74, 161.92, 159.98, 159.45, 146.56, 142.09, 137.82, 137.67, 137.55, 127.90, 127.83, 117.00, 116.83, 113.00, 112.84, 109.59, 76.07, 57.14, 56.29, 39.10, 33.94, 31.48, 19.99, 19.38, 18.82, 18.47, 17.46. 210 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.32 (m, [M + H]⁺ calcd for 2H), 7.16 (dd, J = 9.5, 5.7 Hz, 1H), C₂₇H₃₅FN₂O₇, 6.98 (d, J = 5.5 Hz, 1H), 6.83-6.76 503.2552; found, (m, 2H), 5.10 (dq, J = 8.0, 6.3 Hz, 1H), 503.2554 4.54 (dd, J = 9.4, 4.5 Hz, 1H), 3.88 (s, 3H), 3.19 (p, J = 7.2 Hz, 1H), 2.93 (p, J = 7.0 Hz, 1H), 2.34 (s, 3H), 1.88 (pd, J = 6.9, 4.5 Hz, 1H), 1.34 (d, J = 7.0 Hz, 6H), 1.25 (d, J = 6.3 Hz, 3H), 1.21 (d, J = 7.1 Hz, 3H), 0.81 (d, J = 6.9 Hz, 3H), 0.63 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.66, 171.16, 162.69, 161.96, 160.03, 159.41, 146.55, 142.06, 138.40, 138.34, 137.62, 137.32, 127.61, 116.73, 116.57, 112.86, 112.70, 109.54, 75.49, 56.79, 56.28, 38.77, 33.92, 31.34, 19.89, 19.01, 18.82, 17.63, 17.17, 17.05. 211 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.38- [M + H]⁺ calcd for 8.27 (m, 2H), 7.21 (dd, J = 7.8, 1.3 Hz, C₂₅H₃₆N₂O₆, 1H), 7.09 (dddd, J = 23.7, 14.5, 7.3, 1.6 485.2646; found, Hz, 3H), 6.97 (d, J = 5.5 Hz, 1H), 5.14 485.2642 (dq, J = 6.8, 5.8, 5.3 Hz, 1H), 4.54 (dd, J = 9.5, 4.4 Hz, 1H), 3.88 (s, 3H), 3.26 (dp, J = 14.6, 7.1 Hz, 1H), 2.93 (p, J = 6.9 Hz, 1H), 2.36 (d, J = 3.7 Hz, 3H), 1.85 (pd, J = 6.9, 4.4 Hz, 1H), 1.34 (d, J = 7.0 Hz, 6H), 1.27 (d, J = 6.3 Hz, 3H), 1.23 (d, J = 7.1 Hz, 3H), 0.78 (d, J = 6.9 Hz, 3H), 0.58 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.65, 171.20, 162.68, 159.38, 146.55, 142.13, 141.63, 137.58, 136.06, 130.25, 126.19, 126.05, 109.49, 75.58, 56.75, 56.29, 39.27, 33.92, 31.33, 19.82, 19.02, 18.81, 17.57, 17.02, 16.89. 212 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.42 (d, [M + H]⁺ calcd for J = 9.0 Hz, 1H), 8.34 (d, J = 5.5 Hz, C₂₆H₃₃FN₂O₆, 1H), 7.14 (dd, J = 8.6, 5.5 Hz, 2H), 489.2395; found, 7.00 (d, J = 5.5 Hz, 1H), 6.97-6.89 489.2391 (m, 2H), 5.03 (p, J = 6.4 Hz, 1H), 4.65 (dd, J = 9.4, 4.7 Hz, 1H), 3.89 (s, 3H), 3.00-2.85 (m, 2H), 2.25 (pd, J = 6.9, 4.7 Hz, 1H), 1.38-1.31 (m, 6H), 1.28 (d, J = 7.0 Hz, 3H), 1.09 (d, J = 6.3 Hz, 3H), 0.99 (d, J = 6.9 Hz, 3H), 0.91 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.68, 171.17, 162.73, 162.59, 160.64, 159.46, 146.56, 142.06, 138.69, 137.69, 129.27, 129.21, 115.23, 115.07, 109.60, 76.00, 57.13, 56.30, 43.99, 33.94, 31.47, 19.30, 18.81, 18.02, 17.49, 17.14. 213 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.45 (d, [M + H]⁺ calcd for J = 8.6 Hz, 1H), 8.34 (d, J = 5.5 Hz, C₂₈H₃₈N₂O₇, 1H), 7.07 (d, J = 9.4 Hz, 1H), 6.99 (d, 515.2752; found, J = 5.5 Hz, 1H), 6.72-6.65 (m, 2H), 515.2737 5.06 (dq, J = 8.3, 6.2 Hz, 1H), 4.67 (dd, J = 9.3, 4.7 Hz, 1H), 3.89 (s, 3H), 3.76 (s, 3H), 3.16-3.05 (m, 1H), 2.95 (p, J = 7.0 Hz, 1H), 2.35-2.25 (m, 3H), 1.40-1.30 (m, 6H), 1.23 (d, J = 6.9 Hz, 3H), 1.10 (d, J = 6.3 Hz, 3H), 1.01 (d, J = 6.8 Hz, 3H), 0.93 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.67, 171.40, 162.75, 159.43, 157.63, 146.57, 142.14, 137.65, 136.86, 134.14, 127.37, 115.93, 111.45, 109.57, 76.57, 60.39, 57.17, 56.29, 55.12, 39.07, 33.94, 31.51, 20.18, 19.40, 18.82, 18.54, 17.77, 17.48, 14.20. 214 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.44 (d, [M + H]⁺ calcd for J = 9.1 Hz, 1H), 8.35 (d, J = 5.4 Hz, C₂₇H₃₅FN₂O₆, 1H), 7.13 (dd, J = 9.6, 5.8 Hz, 1H), 503.2552; found, 7.00 (d, J = 5.4 Hz, 1H), 6.88-6.78 503.2549 (m, 2H), 5.09 (dq, J = 8.1, 6.3 Hz, 1H), 4.63 (dd, J = 9.1, 5.2 Hz, 1H), 3.89 (s, 3H), 3.13 (p, J = 7.1 Hz, 1H), 2.95 (p, J = 7.0 Hz, 1H), 2.32 (s, 3H), 2.26 (pd, J = 6.8, 4.9 Hz, 1H), 1.41-1.31 (m, 6H), 1.23 (d, J = 6.9 Hz, 3H), 1.11 (d, J = 6.3 Hz, 3H), 0.99 (d, J = 7.0 Hz, 3H), 0.96 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.68, 171.48, 162.75, 161.91, 159.97, 159.44, 146.59, 142.11, 137.84, 137.64, 137.49, 127.88, 116.98, 116.81, 113.04, 112.88, 109.58, 75.80, 57.04, 56.29, 39.14, 33.95, 31.48, 20.01, 19.00, 18.81, 18.26, 17.94, 17.46. 215 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.38- [M + H]⁺ calcd for 8.28 (m, 2H), 7.25-7.20 (m, 1H), 7.16- C₂₇H₃₆N₂O₆, 7.02 (m, 3H), 6.99 (d, J = 5.4 Hz, 485.2646; found, 1H), 5.13 (p, J = 6.4 Hz, 1H), 4.53 (dd, 485.2643 J = 9.1, 4.9 Hz, 1H), 3.89 (s, 3H), 3.28 (p, J = 7.1 Hz, 1H), 2.94 (h, J = 7.0 Hz, 1H), 2.35 (s, 3H), 2.21-2.09 (m, 1H), 1.35 (dd, J = 7.0, 1.2 Hz, 6H), 1.26 (d, J = 7.1 Hz, 3H), 1.21 (d, J = 6.2 Hz, 3H), 0.86 (d, J = 6.9 Hz, 3H), 0.81 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.68, 170.88, 162.55, 159.42, 146.51, 142.10, 141.12, 137.63, 136.16, 130.26, 126.41, 126.19, 126.09, 109.52, 75.28, 57.01, 56.29, 38.91, 33.94, 31.50, 19.81, 18.81, 17.71, 16.90, 16.26. 216 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.48- [M + H]⁺ calcd for 8.39 (m, 1H), 8.34 (d, J = 5.4 Hz, 1H), C₂₆H₃₃FN₂O₆, 7.19-7.11 (m, 2H), 7.03-6.90 (m, 489.2395; found, 3H), 5.05 (m, 1H), 4.62 (dd, J = 9.1, 489.2391 5.1 Hz, 1H), 3.89 (s, 3H), 2.92 (dp, J = 26.1, 7.0 Hz, 2H), 2.25 (pd, J = 6.9, 4.2 Hz, 1H), 1.38-1.32 (m, 6H), 1.27 (d, J = 7.1 Hz, 3H), 1.08 (d, J = 6.2 Hz, 3H), 0.98 (d, J = 6.9 Hz, 3H), 0.95 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.68, 171.37, 162.76, 162.61, 160.67, 159.44, 146.59, 142.08, 138.67, 137.64, 129.32, 129.26, 115.27, 115.10, 109.59, 75.75, 57.06, 56.30, 44.10, 33.95, 31.45, 18.97, 18.81, 17.97, 17.84, 17.27. 217 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.46 (d, [M + H]⁺ calcd for J = 9.0 Hz, 1H), 8.35 (d, J = 5.4 Hz, C₂₈H₃₈N₂O₇, 1H), 7.09 (d, J = 8.4 Hz, 1H), 6.99 (d, 515.2752; found, J = 5.5 Hz, 1H), 6.75-6.66 (m, 2H), 515.2741 5.09 (dq, J = 8.3, 6.2 Hz, 1H), 4.65 (dd, J = 9.1, 5.0 Hz, 1H), 3.89 (s, 3H), 3.75 (s, 3H), 3.16-3.04 (m, 1H), 2.95 (p, J = 7.0 Hz, 1H), 2.31 (s, 3H), 2.27 (qd, J = 6.9, 5.0 Hz, 1H), 1.39-1.32 (m, 6H), 1.22 (d, J = 6.9 Hz, 3H), 1.10 (d, J = 6.3 Hz, 3H), 0.99 (d, J = 6.8 Hz, 3H), 0.96 (d, J = 6.9 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.68, 171.52, 162.73, 159.42, 157.61, 146.60, 142.18, 137.62, 136.92, 134.06, 127.42, 115.96, 111.44, 109.55, 76.31, 57.04, 56.29, 55.10, 39.09, 33.94, 31.54, 20.20, 19.00, 18.82, 18.33, 17.94, 17.77. 218 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.37- [M + H]⁺ calcd for 8.28 (m, 2H), 7.22-7.12 (m, 1H), 6.99 C₂₅H₃₁FN₂O₆, (d, J = 5.5 Hz, 1H), 6.85-6.75 (m, 475.2239; found, 2H), 5.16-5.05 (m, 1H), 4.57 (h, J = 475.2236 7.4 Hz, 1H), 3.89 (s, 3H), 3.22 (pd, J = 7.3, 4.6 Hz, 1H), 3.00-2.89 (m, 1H), 2.33 (s, 3H), 1.39-1.30 (m, 9H), 1.22 (dd, J = 9.8, 6.7 Hz, 6H). ¹³C NMR (126 MHz, CDCl₃) δ 174.70, 171.98, 162.25, 161.93, 159.99, 159.45, 146.51, 141.82, 138.46, 137.69, 136.79, 136.76, 127.85, 127.79, 116.74, 116.58, 112.79, 112.62, 109.59, 75.24, 56.30, 47.88, 38.53, 33.95, 19.88, 18.80, 18.41, 17.05, 16.71. 219 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.48 (d, [M + H]⁺ calcd for J = 6.9 Hz, 1H), 8.33 (d, J = 5.3 Hz, C₂₅H₃₁FN₂O₆, 1H), 7.13 (dd, J = 9.4, 5.8 Hz, 1H), 475.2239; found, 6.99 (d, J = 5.5 Hz, 1H), 6.88-6.81 475.2238 (m, 2H), 5.09 (dp, J = 8.1, 6.5 Hz, 1H), 4.72 (p, J = 7.2 Hz, 1H), 3.89 (s, 3H), 3.14 (p, J = 7.1 Hz, 1H), 2.95 (p, J = 7.0 Hz, 1H), 2.33 (d, J = 2.4 Hz, 3H), 1.49 (d, J = 7.1 Hz, 3H), 1.38-1.33 (m, 6H), 1.23 (d, J = 6.9 Hz, 3H), 1.11 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.71, 172.42, 162.36, 161.94, 159.99, 159.45, 146.58, 141.91, 137.86, 137.80, 137.69, 137.46, 127.91, 127.84, 117.04, 116.87, 113.00, 112.83, 109.62, 75.99, 56.30, 48.11, 39.18, 33.96, 20.00, 19.99, 18.85, 18.81, 18.36, 17.37. 220 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.56 (s, [M + H]⁺ calcd for 1H), 8.35 (d, J = 5.4 Hz, 1H), 7.09 (d, C₂₄H₃₀N₂O₇, J = 8.4 Hz, 1H), 7.02 (d, J = 5.5 Hz, 1H), 459.2126; found, 6.77-6.67 (m, 2H), 5.10 (dq, J = 8.3, 459.2103 6.3 Hz, 1H), 4.72 (tt, J = 8.8, 6.2 Hz, 1H), 3.91 (s, 3H), 3.76 (s, 3H), 3.15- 3.06 (m, 1H), 2.41 (s, 3H), 2.32 (s, 3H), 1.50 (d, J = 7.2 Hz, 3H), 1.22 (d, J = 6.9 Hz, 3H), 1.10 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 170.46, 167.04, 160.48, 157.55, 155.66, 144.77, 139.57, 135.54, 135.03, 132.01, 125.44, 113.97, 109.50, 107.87, 74.52, 54.39, 53.17, 46.15, 37.09, 18.84, 18.30, 16.63, 16.25, 15.80. 221 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.44 (t, [M + H]⁺ calcd for J = 5.4 Hz, 1H), 8.34 (d, J = 5.4 Hz, C₂₄H₂₉FN₂O₆, 1H), 7.12 (ddd, J = 10.1, 6.2, 3.4 Hz, 461.2082; found, 1H), 7.00 (d, J = 5.5 Hz, 1H), 6.90- 461.2080 6.80 (m, 3H), 5.12 (dq, J = 7.7, 6.2 Hz, 1H), 4.18 (dd, J = 5.4, 2.8 Hz, 2H), 3.90 (s, 3H), 3.14 (p, J = 7.1 Hz, 1H), 2.95 (p, J = 7.0 Hz, 1H), 2.32 (s, 3H), 1.37 (d, J = 7.0 Hz, 6H), 1.22 (d, J = 6.9 Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.71, 169.37, 163.02, 161.95, 160.00, 159.48, 146.63, 141.67, 137.91, 137.85, 137.73, 137.32, 127.89, 127.82, 117.05, 116.89, 113.04, 112.87, 109.72, 76.09, 56.31, 41.38, 39.11, 33.98, 20.00, 18.81, 18.71, 18.22, 17.42. 222 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.36- [M + H]⁺ calcd for 8.27 (m, 2H), 7.21 (dd, J = 7.7, 1.4 Hz, C₂₄H₃₀N₂O₆, 1H), 7.16-7.05 (m, 3H), 6.98 (d, J = 443.2177; found, 5.5 Hz, 1H), 5.17 (h, J = 6.6 Hz, 1H), 443.2176 4.13-3.89 (m, 2H), 3.89 (s, 3H), 3.28 (p, J = 7.1 Hz, 1H), 2.94 (p, J = 7.0 Hz, 1H), 2.35 (s, 3H), 1.36 (d, J = 7.0 Hz, 6H), 1.28-1.22 (m, 6H). ¹³C NMR (126 MHz, CDCl₃) δ 174.69, 169.05, 162.90, 159.44, 146.58, 141.67, 141.02, 137.68, 136.17, 130.25, 126.29, 126.27, 126.11, 109.66, 75.58, 56.29, 41.22, 39.09, 33.97, 19.80, 18.81, 17.05, 16.23. 223 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.44 (t, [M + H]⁺ calcd for J = 5.5 Hz, 1H), 8.33 (d, J = 5.4 Hz, C₂₃H₂₇FN₂O₆, 1H), 7.18-7.11 (m, 2H), 7.03-6.92 447.1926; found, (m, 3H), 5.14-5.01 (m, 1H), 4.17 (d, 447.1923 J = 5.4 Hz, 2H), 3.90 (s, 3H), 3.00-2.86 (m, 2H), 1.37 (d, J = 7.0 Hz, 6H), 1.27 (d, J = 7.0 Hz, 3H), 1.09 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.72, 169.28, 163.04, 162.64, 160.69, 159.48, 146.62, 141.66, 138.52, 137.74, 129.30, 129.24, 115.31, 115.14, 109.73, 76.02, 56.31, 44.12, 41.41, 33.98, 18.81, 17.81, 17.26. 224 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.45 (t, [M + H]⁺ calcd for J = 5.4 Hz, 1H), 8.33 (d, J = 5.4 Hz, C₂₅H₃₂N₂O₇, 1H), 7.08 (d, J = 8.5 Hz, 1H), 7.00 (d, 473.2282; found, J = 5.5 Hz, 1H), 6.76-6.67 (m, 2H), 473.2282 5.12 (dq, J = 8.3, 6.3 Hz, 1H), 4.24- 4.14 (m, 2H), 3.89 (s, 3H), 3.77 (s, 3H), 3.16-3.05 (m, 1H), 2.96 (p, J = 7.0 Hz, 1H), 2.31 (s, 3H), 1.37 (d, J = 7.0 Hz, 6H), 1.22 (d, J = 6.9 Hz, 3H), 1.12 (d, J = 6.2 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.71, 169.43, 163.01, 159.46, 157.66, 146.63, 141.71, 137.71, 136.96, 133.86, 127.39, 115.94, 111.46, 109.70, 76.54, 56.30, 55.11, 41.41, 39.04, 33.98, 20.18, 18.81, 18.27, 17.62. 225 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.39- [M + H]⁺ calcd for 8.28 (m, 2H), 7.24-7.17 (m, 1H), 7.16- C₂₅H₃₂N₂O₆, 7.02 (m, 3H), 6.98 (d, J = 5.5 Hz, 457.2333; found, 1H), 5.14 (p, J = 6.6 Hz, 1H), 4.55 (dt, 457.2327 J = 10.4, 7.4 Hz, 1H), 3.89 (s, 3H), 3.28 (p, J = 7.1 Hz, 1H), 2.94 (p, J = 6.9 Hz, 1H), 2.36 (d, J = 4.9 Hz, 3H), 1.36 (dd, J = 7.0, 1.6 Hz, 6H), 1.31 (d, J = 7.1 Hz, 3H), 1.25 (d, J = 7.2 Hz, 3H), 1.22 (d, J = 6.4 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.70, 171.96, 162.25, 159.42, 146.50, 141.92, 141.08, 137.65, 136.14, 130.23, 126.33, 126.21, 126.09, 109.55, 75.32, 56.29, 47.95, 39.03, 33.95, 19.82, 18.80, 18.47, 16.95, 16.35. 226 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.44 (s, [M + H]⁺ calcd for 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.20- C₂₄H₂₉FN₂O₆, 7.12 (m, 2H), 7.02-6.93 (m, 3H), 5.07- 461.2082; found, 4.97 (m, 1H), 4.70 (p, J = 7.2 Hz, 461.2078 1H), 3.90 (s, 3H), 3.01-2.86 (m, 2H), 1.47 (d, J = 7.1 Hz, 3H), 1.39-1.34 (m, 6H), 1.27 (d, J = 7.0 Hz, 3H), 1.07 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.72, 172.36, 162.62, 162.44, 160.67, 159.46, 146.57, 141.88, 138.56, 137.70, 129.33, 129.26, 115.28, 115.11, 109.63, 75.77, 56.30, 48.03, 44.07, 33.96, 18.81, 18.46, 17.65, 17.30. 227 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.49 (d, [M + H]⁺ calcd for J = 8.6 Hz, 1H), 8.34 (d, J = 5.4 Hz, C₂₆H₃₄N₂O₇, 1H), 7.09 (d, J = 8.3 Hz, 1H), 6.99 (d, 487.2439; found, J = 5.4 Hz, 1H), 6.75-6.64 (m, 2H), 487.2425 5.09 (dq, J = 8.3, 6.2 Hz, 1H), 4.72 (p, J = 7.2 Hz, 1H), 3.89 (s, 3H), 3.76 (s, 3H), 3.16-3.05 (m, 1H), 2.96 (p, J = 7.0 Hz, 1H), 2.32 (s, 3H), 1.49 (d, J = 7.1 Hz, 3H), 1.39-1.34 (m, 6H), 1.21 (d, J = 6.8 Hz, 3H), 1.09 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.71, 172.49, 162.41, 159.44, 157.62, 146.58, 141.97, 137.67, 136.95, 134.01, 127.40, 115.94, 111.45, 109.59, 76.36, 56.29, 55.11, 48.06, 39.08, 33.96, 20.21, 18.82, 18.58, 18.19, 17.74. 228 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.40- [M + H]⁺ calcd for 8.33 (m, 1H), 8.31 (d, J = 5.4 Hz, 1H), C₂₅H₃₂N₂O₆, 7.22-7.15 (m, 1H), 7.15-7.03 (m, 457.2333; found, 3H), 6.97 (d, J = 5.4 Hz, 1H), 5.15 (dq, 457.2329 J = 8.0, 6.2 Hz, 1H), 4.61-4.47 (m, 1H), 3.88 (s, 3H), 3.25 (p, J = 7.3 Hz, 1H), 2.93 (p, J = 7.0 Hz, 1H), 2.36 (d, J = 3.5 Hz, 3H), 1.35 (d, J = 7.0 Hz, 6H), 1.28 (d, J = 6.3 Hz, 3H), 1.24 (d, J = 7.0 Hz, 3H), 1.01 (d, J = 7.2 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.68, 172.25, 162.26, 159.39, 146.54, 141.96, 141.54, 137.60, 136.03, 130.21, 126.16, 125.98, 109.53, 75.56, 56.27, 47.84, 39.43, 33.93, 19.84, 18.80, 17.71, 17.01. 229 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.46 (d, [M + H]⁺ calcd for J = 8.6 Hz, 1H), 8.33 (d, J = 5.4 Hz, C₂₄H₂₉FN₂O₆, 1H), 7.18-7.10 (m, 2H), 7.01-6.89 461.2082; found, (m, 3H), 5.09-5.00 (m, 1H), 4.71 (p, 461.2077 J = 7.3 Hz, 1H), 3.89 (d, J = 1.2 Hz, 3H), 3.01-2.86 (m, 2H), 1.47 (dd, J = 7.2, 1.8 Hz, 3H), 1.39-1.34 (m, 6H), 1.27 (dd, J = 7.1, 1.6 Hz, 3H), 1.09 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.71, 172.29, 162.61, 162.36, 160.66, 159.46, 146.57, 141.89, 138.63, 137.70, 129.33, 129.29, 129.26, 115.27, 115.10, 109.63, 75.95, 56.30, 48.10, 44.13, 33.96, 18.81, 18.71, 17.93, 17.20. 230 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.50 (d, [M + H]⁺ calcd for J = 8.7 Hz, 1H), 8.33 (d, J = 5.4 Hz, C₂₆H₃₄N₂O₇, 1H), 7.09 (d, J = 8.3 Hz, 1H), 6.99 (d, 487.2439; found, J = 5.5 Hz, 1H), 6.77-6.66 (m, 2H), X487.2423 5.08 (dq, J = 8.3, 6.2 Hz, 1H), 4.73 (p, J = 7.2 Hz, 1H), 3.89 (s, 3H), 3.77 (s, 3H), 3.17-3.05 (m, 1H), 2.95 (p, J = 7.0 Hz, 1H), 2.32 (s, 3H), 1.50 (d, J = 7.2 Hz, 3H), 1.38-1.33 (m, 6H), 1.22 (d, J = 6.9 Hz, 3H), 1.11 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 174.71, 172.49, 162.36, 159.43, 157.65, 146.58, 141.97, 137.67, 136.91, 134.03, 127.40, 115.92, 111.45, 109.59, 76.46, 56.29, 55.12, 48.15, 39.14, 33.95, 20.19, 18.79, 18.43, 17.63. 231 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.26 (d, [M + H]⁺ calcd for J = 5.4 Hz, 1H), 8.22 (t, J = 7.4 Hz, C₂₄H₃₀N₂O₇, 1H), 7.22-7.03 (m, 4H), 6.93 (d, J = 459.2126; found, 5.4 Hz, 1H), 5.73 (dd, J = 5.6, 1.8 Hz, 459.2121 2H), 5.16 (dq, J = 8.1, 6.3 Hz, 1H), 4.58-4.51 (m, 1H), 3.90 (s, 3H), 3.31- 3.22 (m, 1H), 2.37 (s, 3H), 2.06 (s, 3H), 1.31 (d, J = 6.2 Hz, 3H), 1.24 (d, J = 7.0 Hz, 3H), 1.03 (d, J = 7.2 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 172.26, 170.26, 162.87, 160.25, 145.68, 143.94, 142.57, 141.57, 136.03, 130.21, 126.16, 125.94, 109.49, 89.57, 75.57, 56.16, 48.08, 39.48, 20.87, 19.84, 17.92, 17.77, 17.05. 232 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.33 (d, [M + H]⁺ calcd for J = 7.4 Hz, 1H), 8.29 (d, J = 5.3 Hz, C₂₃H₂₇FN₂O₇, 1H), 7.20-7.12 (m, 2H), 7.01-6.93 463.1875; found, (m, 3H), 5.79-5.71 (m, 2H), 5.10- 463.1870 5.00 (m, 1H), 4.73 (p, J = 7.2 Hz, 1H), 3.92 (d, J = 2.0 Hz, 3H), 2.92 (p, J = 7.1 Hz, 1H), 2.07 (d, J = 1.6 Hz, 3H), 1.50 (d, J = 7.1 Hz, 3H), 1.29 (dd, J = 7.0, 2.5 Hz, 3H), 1.08 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 172.37, 170.29, 163.02, 162.63, 160.68, 160.30, 145.74, 144.03, 142.51, 138.55, 138.52, 129.32, 129.26, 115.30, 115.13, 109.59, 89.58, 75.82, 56.20, 48.22, 44.12, 20.88, 18.39, 17.69, 17.39. 233 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.38 (d, [M + H]⁺ calcd for J = 7.7 Hz, 1H), 8.29 (d, J = 5.3 Hz, C₂₅H₃₂N₂O₈, 1H), 7.09 (d, J = 8.3 Hz, 1H), 6.96 (d, 489.2231; found, J = 5.3 Hz, 1H), 6.79-6.62 (m, 2H), 489.2220 5.76 (d, J = 2.2 Hz, 2H), 5.17-5.05 (m, 1H), 4.75 (p, J = 7.2 Hz, 1H), 3.92 (s, 3H), 3.76 (s, 3H), 3.22-3.03 (m, 1H), 2.32 (s, 3H), 2.07 (s, 3H), 1.52 (d, J = 7.2 Hz, 3H), 1.23 (d, J = 6.9 Hz, 3H), 1.10 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 172.52, 170.29, 162.99, 160.29, 157.63, 145.74, 144.02, 142.57, 136.96, 133.96, 127.39, 115.93, 111.48, 109.55, 89.61, 76.42, 56.19, 55.11, 48.23, 39.10, 20.88, 20.21, 18.51, 18.21, 17.82. 234 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.50 (d, film) 3383, [M + H]⁺ calcd for J = 7.4 Hz, 1H), 8.34 (d, J = 5.4 Hz, 2981, 1737, C₂₅H₃₀F₃N₂O₆, 1H), 7.64 (dd, J = 8.0, 1.3 Hz, 1H), 1679, 1505, 511.2050; found, 7.54-7.47 (m, 1H), 7.44 (d, J = 7.8 1310, 1114, 511.2048 Hz, 1H), 7.31 (t, J = 7.5 Hz, 1H), 6.99 1045, 732 (d, J = 5.4 Hz, 1H), 5.26-5.11 (m, cm⁻¹ 1H), 4.76 (p, J = 7.3 Hz, 1H), 3.89 (s, 3H), 3.34 (p, J = 6.6 Hz, 1H), 2.96 (hept, J = 7.0 Hz, 1H), 1.54 (d, J = 7.2 Hz, 3H), 1.36 (dd, J = 7.0, 1.3 Hz, 6H), 1.28 (d, J = 6.8 Hz, 3H), 1.10 (d, J = 6.3 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −58.25. 235 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.47 (d, film) 3383, [M + H]⁺ calcd for J = 8.1 Hz, 1H), 8.34 (d, J = 5.4 Hz, 2982, 1761, C₂₅H₂₉F₄N₂O₆, 1H), 7.42 (dd, J = 8.8, 5.4 Hz, 1H), 1738, 1679, 529.1956; found, 7.34 (dd, J = 9.2, 2.8 Hz, 1H), 7.21 (td, 1500, 1312, 529.1954 J = 8.3, 2.8 Hz, 1H), 7.00 (d, J = 5.5 1119, 909, Hz, 1H), 5.13 (p, J = 6.5 Hz, 1H), 4.75 732 cm⁻¹ (dq, J = 9.3, 7.3 Hz, 1H), 3.89 (s, 3H), 3.36-3.24 (m, 1H), 2.95 (hept, J = 7.0 Hz, 1H), 1.53 (d, J = 7.2 Hz, 3H), 1.36 (dd, J = 7.0, 1.5 Hz, 6H), 1.26 (d, J = 6.8 Hz, 3H), 1.11 (d, J = 6.2 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −58.80, −114.13. 236 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.53 (d, film) 3383, [M + H]⁺ calcd for J = 7.7 Hz, 1H), 8.32 (d, J = 5.4 Hz, 2943, 1763, C₂₃H₃₅N₂O₆, 1H), 6.98 (d, J = 5.4 Hz, 1H), 5.08 (qd, 1733, 1678, 435.2490; found, J = 6.5, 3.0 Hz, 1H), 4.69 (dt, J = 7.9, 1504, 1310, 435.2483 7.0 Hz, 1H), 3.89 (s, 3H), 3.02-2.87 1210, 1090, (m, 1H), 1.74 (dddd, J = 19.4, 17.2, 843, 731 9.8, 5.1 Hz, 3H), 1.67-1.51 (m, 4H), cm⁻¹ 1.48 (d, J = 7.1 Hz, 3H), 1.36 (d, J = 7.0 Hz, 6H), 1.22 (d, J = 6.4 Hz, 3H), 1.18-1.02 (m, 3H), 0.94 (d, J = 6.9 Hz, 3H). 237 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.52 (s, film) 3382, [M + H]⁺ calcd for 1H), 8.34 (d, J = 5.4 Hz, 1H), 7.04- 2976, 1762, C₂₆H₃₄N₂O₆, 6.91 (m, 4H), 5.60 (dp, J = 10.5, 6.3 1734, 1678, 471.2490; found, Hz, 1H), 4.84-4.67 (m, 1H), 3.89 (s, 1504, 1210, 471.2488 3H), 3.42 (dp, J = 10.6, 7.1 Hz, 1H), 1079, 730 2.95 (hept, J = 7.0 Hz, 1H), 2.41 (d, J = cm⁻¹ 2.5 Hz, 3H), 2.37 (s, 3H), 1.55 (dd, J = 14.2, 7.1 Hz, 3H), 1.40-1.32 (m, 6H), 1.28 (d, J = 7.1 Hz, 3H), 1.03 (dd, J = 6.2, 3.0 Hz, 3H). 238 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.52 (d, film) 3384, [M + H]⁺ calcd for J = 10.1 Hz, 1H), 8.34 (d, J = 5.4 Hz, 2977, 1762, C₂₆H₃₄FN₂O₆, 1H), 6.99 (d, J = 5.4 Hz, 1H), 6.70 1735, 1679, 489.2395; found, (ddd, J = 15.3, 9.4, 2.7 Hz, 2H), 5.56 1505, 1211, 489.2399 (dp, J = 10.4, 6.3 Hz, 1H), 4.82-4.65 1127, 861, (m, 1H), 3.89 (s, 3H), 3.43-3.20 (m, 731 cm⁻¹ 1H), 2.95 (hept, J = 7.0 Hz, 1H), 2.40 (d, J = 2.4 Hz, 3H), 2.35 (s, 3H), 1.54 (dd, J = 13.5, 7.2 Hz, 3H), 1.36 (dd, J = 7.1, 1.6 Hz, 6H), 1.26 (dd, J = 7.2, 1.0 Hz, 3H), 1.02 (dd, J = 62, 2.9 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −118.50 (d, J = 25.8 Hz). 239 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.47 (d, film) 3383, [M + H]⁺ calcd for J = 7.8 Hz, 1H), 8.33 (d, J = 5.4 Hz, 2982, 1762, C₂₅H₃₀F₃N₂O₆, 1H), 7.67-7.60 (m, 1H), 7.54-7.45 1739, 1681, 511.2050; found, (m, 1H), 7.44 (d, J = 7.8 Hz, 1H), 7.34- 1505, 1311, 511.2052 7.27 (m, 1H), 6.99 (d, J = 5.5 Hz, 1151, 1117, 1H), 5.25-5.14 (m, 1H), 4.81-4.69 772 cm⁻¹ (m, 1H), 3.89 (s, 3H), 3.40-3.25 (m, 1H), 2.96 (hept, J = 7.0 Hz, 1H), 1.51 (d, J = 7.1 Hz, 3H), 1.37 (dd, J = 7.0, 1.8 Hz, 6H), 1.29 (d, J = 6.8 Hz, 3H), 1.09 (d, J = 6.3 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −58.26. 240 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.44 (d, film) 3383, [M + H]⁺ calcd for J = 7.8 Hz, 1H), 8.33 (d, J = 5.4 Hz, 2982, 1761, C₂₅H₂₉F₄N₂O₆, 1H), 7.42 (dd, J = 8.8, 5.4 Hz, 1H), 1740, 1680, 529.1956; found, 7.33 (dd, J = 9.2, 2.8 Hz, 1H), 7.19 (td, 1500, 1312, 529.1958 J = 8.3, 2.8 Hz, 1H), 7.00 (d, J = 5.4 1120, 909, Hz, 1H), 5.14 (p, J = 6.5 Hz, 1H), 4.81- 732 cm⁻¹ 4.67 (m, 1H), 3.90 (s, 3H), 3.36- 3.22 (m, 1H), 2.96 (hept, J = 7.0 Hz, 1H), 1.50 (d, J = 7.2 Hz, 3H), 1.37 (dd, J = 7.0, 1.9 Hz, 6H), 1.28 (d, J = 6.9 Hz, 3H), 1.11 (d, J = 6.3 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −58.80, −114.24. 241 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.52 (s, film) 3382, [M + H]⁺ calcd for 1H), 8.32 (d, J = 5.4 Hz, 1H), 6.98 (d, 2944, 1764, C₂₃H₃₅N₂O₆, J = 5.4 Hz, 1H), 5.07 (qd, J = 6.5, 3.0 1734, 1680, 435.2490; found, Hz, 1H), 4.73-4.62 (m, 1H), 3.89 (s, 1504, 1210, 435.2491 3H), 2.95 (hept, J = 7.0 Hz, 1H), 1.85- 1090, 1040, 1.61 (m, 2H), 1.61-1.50 (m, 2H), 1.47 916, 843, (d, J = 7.1 Hz, 3H), 1.43-1.29 (m, 732 cm⁻¹ 9H), 1.21 (d, J = 6.4 Hz, 3H), 1.17- 1.01 (m, 3H), 0.93 (d, J = 6.9 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 174.69, 172.36, 162.38, 159.45, 146.55, 142.04, 137.69, 109.56, 74.50, 56.28, 48.04, 43.14, 42.93, 33.98, 31.24, 30.70, 25.13, 25.01, 18.82, 18.71, 17.48, 12.50. 242 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.49 (d, film) 3383, [M + H]⁺ calcd for J = 8.4 Hz, 1H), 8.34 (d, J = 5.5 Hz, 2977, 1762, C₂₆H₃₄FN₂O₆, 1H), 6.99 (d, J = 5.5 Hz, 1H), 6.70 1735, 1679, 489.2395; found, (ddd, J = 17.0, 9.4, 2.8 Hz, 2H), 5.57 1504, 1210, 489.2399 (dq, J = 10.4, 6.4 Hz, 1H), 4.85-4.62 1081, 914, (m, 1H), 3.89 (s, 3H), 3.36 (dp, J = 861, 731 10.4, 7.1 Hz, 1H), 2.95 (hept, J = 7.0 cm⁻¹ Hz, 1H), 2.40 (s, 3H), 2.35 (s, 3H), 1.52 (d, J = 7.2 Hz, 3H), 1.36 (dd, J = 7.0, 1.9 Hz, 6H), 1.26 (dd, J = 7.2, 1.0 Hz, 3H), 1.02 (d, J = 6.2 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −118.53. 243 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.54 (d, film) 3383, [M + H]⁺ calcd for J = 12.1 Hz, 1H), 8.34 (d, J = 5.4 Hz, 2977, 1763, C₂₆H₃₅N₂O₆, 1H), 7.04-6.94 (m, 4H), 5.60 (dp, J = 1735, 1679, 471.2490; found, 10.4, 6.3 Hz, 1H), 4.75 (ddq, J = 14.6, 1504, 1211, 471.2495 7.2, 3.5 Hz, 1H), 3.89 (s, 3H), 3.42 (dp, 1080, 914, J = 10.6, 7.1 Hz, 1H), 2.96 (hept, J = 731 cm⁻¹ 7.0 Hz, 1H), 2.41 (d, J = 2.5 Hz, 3H), 2.38 (s, 3H), 1.55 (dd, J = 14.2, 7.1 Hz, 3H), 1.36 (dd, J = 7.1, 1.7 Hz, 6H), 1.28 (d, J = 7.1 Hz, 3H), 1.03 (dd, J = 6.2, 2.9 Hz, 3H). 244 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.49 (d, film) 3383, [M + H]⁺ calcd for J = 9.5 Hz, 1H), 8.34 (d, J = 5.4 Hz, 2977, 1761, C₂₆H₃₄FN₂O₆, 1H), 6.99 (d, J = 5.5 Hz, 1H), 6.82- 1735, 1678, 489.2395; found, 6.61 (m, 2H), 5.56 (dp, J = 10.4, 6.3 1504, 1309, 489.2399 Hz, 1H), 4.75 (pd, J = 7.2, 4.4 Hz, 1H), 1209, 1081, 3.89 (s, 3H), 3.36 (dp, J = 10.3, 7.0 Hz, 1059, 731 1H), 2.95 (p, J = 7.0 Hz, 1H), 2.40 (d, cm⁻¹ J = 2.4 Hz, 3H), 2.35 (s, 3H), 1.54 (dd, J = 13.6, 7.2 Hz, 3H), 1.36 (dd, J = 7.0, 1.8 Hz, 6H), 1.26 (dd, J = 7 2, 1.1 Hz, 3H), 1.02 (dd, J = 62, 2.9 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −118.49 (d, J = 25.8 Hz). 245 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.56 (d, film) 3379, [M + H]⁺ calcd for J = 7.5 Hz, 1H), 8.35 (d, J = 5.5 Hz, 2986, 1771, C₂₃H₂₆F₃N₂O₆, 1H), 7.64 (dd, J = 8.0, 1.4 Hz, 1H), 1736, 1676, 473.1737; found, 7.55-7.46 (m, 1H), 7.43 (d, J = 7.8 1508, 1310, 483.1733 Hz, 1H), 7.35-7.28 (m, 1H), 7.01 (d, 1149, 1116, J = 5.5 Hz, 1H), 5.25-5.13 (m, 1H), 1046, 732 4.81-4.70 (m, 1H), 3.91 (s, 3H), 3.43- cm⁻¹ 3.29 (m, 1H), 2.40 (s, 3H), 1.55 (d, J = 7.2 Hz, 3H), 1.28 (d, J = 6.8 Hz, 3H), 1.10 (d, J = 6.3 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −58.25. 246 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.61- film) 3379, [M + H]⁺ calcd for 8.44 (m, 1H), 8.35 (d, J = 5.4 Hz, 1H), 2986, 1771, C₂₃H₂₅F₄N₂O₆, 7.42 (dd, J = 8.8, 5.3 Hz, 1H), 7.34 (dd, 1737, 1677, 501.1643; found, J = 9.2, 2.9 Hz, 1H), 7.21 (td, J = 8.2, 1500, 1312, 501.1642 2.8 Hz, 1H), 7.02 (d, J = 5.5 Hz, 1H), 1154, 1123, 5.19-5.07 (m, 1H), 4.82-4.69 (m, 1045, 909, 1H), 3.91 (s, 3H), 3.37-3.23 (m, 1H), 732 cm⁻¹ 2.41 (s, 3H), 1.54 (d, J = 7.2 Hz, 3H), 1.27 (d, J = 6.8 Hz, 3H), 1.11 (d, J = 62 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −58.80, −114.08. 247 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.58 (s, film) 3379, [M + H]⁺ calcd for 1H), 8.33 (d, J = 5.5 Hz, 1H), 7.00 (d, 2946, 1771, C₂₁H₃₁N₂O₆, J = 5.5 Hz, 1H), 5.09 (qd, J = 6.5, 3.0 1732, 1676, 407.2177; found, Hz, 1H), 4.77-4.62 (m, 1H), 3.90 (s, 1506, 1310, 407.2173 3H), 2.40 (s, 3H), 1.83-1.68 (m, 3H), 1193, 1174, 1.59 (dddt, J = 19.6, 14.7, 7.5, 3.1 Hz, 1060, 906, 4H), 1.49 (d, J = 7.2 Hz, 3H), 1.38 731 cm⁻¹ (dddd, J = 13.6, 9.7, 6.8, 3.0 Hz, 1H), 1.22 (d, J = 6.5 Hz, 3H), 1.18-1.02 (m, 2H), 0.95 (d, J = 6.8 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 172.30, 168.88, 162.36, 159.48, 146.65, 141.67, 137.52, 109.73, 74.49, 56.28, 48.23, 43.34, 43.11, 31.23, 30.75, 25.16, 24.98, 20.75, 18.87, 17.79, 12.49. 248 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.59 (d, film) 3378, [M + H]⁺ calcd for J = 7.7 Hz, 1H), 8.35 (d, J = 5.4 Hz, 2980, 1770, C₂₄H₃₁N₂O₆, 1H), 7.07-6.91 (m, 4H), 5.67-5.55 1733, 1676, 443.2177; found, (m, 1H), 4.85-4.70 (m, 1H), 3.91 (s, 1506, 1310, 443.2176 3H), 3.42 (dp, J = 10.6, 7.1 Hz, 1H), 1195, 1175, 2.41 (s, 3H), 1.56 (dd, J = 14.4, 7.1 Hz, 1006, 907, 3H), 1.28 (d, J = 7.1 Hz, 3H), 1.04 (dd, 730 cm⁻¹ J = 6.2, 2.8 Hz, 3H). 249 HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.57 (d, [M + H]⁺ calcd for J = 8.7 Hz, 1H), 8.35 (d, J = 5.5 Hz, C₂₄H₃₀FN₂O₆, 1H), 7.01 (d, J = 5.5 Hz, 1H), 6.70 461.2082; found, (ddd, J = 15.2, 9.3, 2.5 Hz, 2H), 5.65- 461.2080 5.47 (m, 1H), 4.81-4.64 (m, 1H), 3.91 (s, 3H), 3.36 (dp, J = 10.5, 7.0 Hz, 1H), 2.40 (s, 6H), 2.35 (s, 3H), 1.55 (dd, J = 13.8, 7.2 Hz, 3H), 1.26 (d, J = 7.2 Hz, 3H), 1.03 (dd, J = 6.2, 2.7 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −118.43. 250 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.54 (d, film) 3377, [M + H]⁺ calcd for J = 7.8 Hz, 1H), 8.34 (d, J = 5.4 Hz, 2985, 1771, C₂₃H₂₆F₃N₂O₆, 1H), 8.01 (d, J = 5.2 Hz, OH), 7.63 (dt, 1737, 1677, 483.1737; found, J = 8.0, 1.7 Hz, 1H), 7.55-7.47 (m, 1507, 1310, 483.1735 1H), 7.44 (d, J = 7.8 Hz, 1H), 7.31 (dt, 1149, 1116, J = 9.6, 4.2 Hz, 1H), 7.01 (d, J = 5.5 771, 731 Hz, 1H), 5.28-5.12 (m, 1H), 4.75 cm⁻¹ (dqd, J = 8.4, 7.2, 1.3 Hz, 1H), 3.91 (s, 3H), 3.41-3.28 (m, 1H), 2.41 (s, 3H), 1.52 (d, J = 7.2 Hz, 3H), 1.29 (d, J = 6.8 Hz, 3H), 1.13-1.05 (m, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −58.25. 251 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.50 (d, film) 2985, [M + H]⁺ calcd for J = 7.9 Hz, 1H), 8.34 (d, J = 5.4 Hz, 1771, 1738, C₂₃H₂₅F₄N₂O₆, 1H), 7.43 (dd, J = 8.8, 5.3 Hz, 1H), 1677, 1500, 501.1643; found, 7.34 (dd, J = 9.2, 2.8 Hz, 1H), 7.20 (td, 1312, 1193, 501.1640 J = 8.2, 2.9 Hz, 1H), 7.02 (d, J = 5.5 1154, 1122, Hz, 1H), 5.15 (h, J = 6.5 Hz, 1H), 4.74 909, 732 (dq, J = 8.1, 7.1 Hz, 1H), 3.92 (s, 3H), cm⁻¹ 3.30 (p, J = 6.9 Hz, 1H), 2.41 (s, 3H), 1.52 (d, J = 7.2 Hz, 3H), 1.28 (d, J = 6.8 Hz, 3H), 1.11 (d, J = 6.3 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −58.80, −114.19. 252 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.58 (s, film) 3382, [M + H]⁺ calcd for 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.00 (d, 2947, 1771, C₂₁H₃₁N₂O₆, J = 5.4 Hz, 1H), 5.08 (qd, J = 6.4, 3.0 1732, 1676, 407.2177; found, Hz, 1H), 4.75-4.63 (m, 1H), 3.91 (s, 1505, 1310, 407.2176 3H), 2.40 (s, 3H), 1.85-1.63 (m, 4H), 1199, 1174, 1.63-1.51 (m, 2H), 1.48 (d, J = 7.2 1151, 1061, Hz, 3H), 1.45-1.32 (m, 2H), 1.21 (d, 906, 731 J = 6.4 Hz, 3H), 1.17-1.00 (m, 2H), cm⁻¹ 0.94 (d, J = 6.9 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 172.27, 168.90, 162.40, 159.48, 146.66, 141.66, 137.53, 109.72, 74.58, 56.28, 48.07, 43.13, 42.93, 31.25, 30.69, 25.14, 25.01, 20.75, 18.69, 17.48, 12.50. 253 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.59 (d, film) 3378, [M + H]⁺ calcd for J = 8.8 Hz, 1H), 8.35 (d, J = 5.4 Hz, 2979, 1770, C₂₄H₃₁N₂O₆, 1H), 7.08-6.92 (m, 4H), 5.66-5.55 1733, 1676, 443.2177; found, (m, 1H), 4.76 (p, J = 7.3 Hz, 1H), 3.91 1506, 1195, 443.2170 (s, 3H), 3.42 (dp, J = 10.5, 7.1 Hz, 1H), 1175, 1006, 2.41 (d, J = 1.7 Hz, 6H), 2.38 (s, 3H), 907, 730 1.54 (d, J = 7.1 Hz, 3H), 1.28 (d, J = cm⁻¹ 7.2 Hz, 3H), 1.03 (d, J = 6.2 Hz, 3H). 254 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.55 film) 3379, [M + H]⁺ calcd for (dd, J = 16.7, 7.9 Hz, 1H), 8.35 (d, J = 2980, 1771, C₂₄H₃₀FN₂O₆, 5.4 Hz, 1H), 7.01 (d, J = 5.5 Hz, 1H), 1733, 1676, 461.2082; found, 6.70 (ddd, J = 17.0, 9.3, 2.7 Hz, 2H), 1507, 1174, 461.2082 5.57 (dq, J = 10.3, 6.1 Hz, 1H), 4.82- 1130, 1007, 4.69 (m, 1H), 3.91 (s, 3H), 3.36 (dp, 731 cm⁻¹ J = 10.5, 6.9 Hz, 1H), 2.40 (d, J = 2.6 Hz, 6H), 2.35 (s, 3H), 1.53 (d, J = 7.2 Hz, 3H), 1.26 (d, J = 7.1 Hz, 3H), 1.02 (d, J = 6.3 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −118.49. 255 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.64- film) 3380, [M + H]⁺ calcd for 8.52 (m, 1H), 8.35 (d, J = 5.4 Hz, 1H), 2979, 1770, C₂₄H₃₁N₂O₆, 7.07-6.90 (m, 4H), 5.68-5.53 (m, 1733, 1676, 443.2177; found, 1H), 4.86-4.68 (m, 1H), 3.91 (s, 3H), 1506, 1310, 443.2176 3.42 (dp, J = 10.5, 7.1 Hz, 1H), 2.42- 1195, 1175, 2.39 (m, 6H), 2.38 (s, 3H), 1.56 (dd, 1006, 907, J = 14.5, 7.1 Hz, 3H), 1.28 (d, J = 7.1 730 cm⁻¹ Hz, 3H), 1.04 (dd, J = 6.2, 2.8 Hz, 3H). 256 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.68- film) 3377, [M + H]⁺ calcd for 8.47 (m, 1H), 8.35 (d, J = 5.4 Hz, 1H), 2981, 1771, C₂₄H₃₀FN₂O₆, 7.01 (d, J = 5.5 Hz, 1H), 6.70 (ddd, J = 1734, 1676, 461.2082; found, 14.7, 9.4, 2.4 Hz, 2H), 5.66-5.48 (m, 1507, 1310, 461.2084 1H), 4.75 (tdd, J = 8.8, 7.2, 5.7 Hz, 1195, 1175, 1H), 3.91 (d, J = 1.6 Hz, 3H), 3.36 (dp, 1007, 908, J = 10.5, 7.0 Hz, 1H), 2.40 (d, J = 2.8 731 cm⁻¹ Hz, 6H), 2.35 (s, 3H), 1.55 (dd, J = 13.9, 7.2 Hz, 3H), 1.26 (d, J = 7.1 Hz, 3H), 1.03 (dd, J = 62, 2.7 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −118.43, −118.49. 257 HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 8.46 (d, [M + H]⁺ calcd for J = 7.4 Hz, 1H), 8.31 (d, J = 5.5 Hz, C₂₃H₂₉N₂O₇, 1H), 7.20-7.10 (m, 2H), 6.98 (d, J = 445.1969; found, 5.5 Hz, 1H), 6.88-6.79 (m, 2H), 5.27 445.1949 (dq, J = 7.7, 6.3 Hz, 1H), 4.61-4.51 (m, 1H), 3.88 (s, 3H), 3.80 (s, 3H), 3.49-3.41 (m, 1H), 2.38 (s, 3H), 1.24 (d, J = 4.7 Hz, 3H), 1.22 (d, J = 3.8 Hz, 3H), 1.11 (d, J = 7.2 Hz, 3H). ¹³CNMR(101 MHz, CDCl₃) δ 172.1, 168.9, 162.3, 159.4, 157.2, 146.6, 141.7, 137.5, 131.2, 128.1, 127.3, 120.5, 110.5, 109.7, 74.9, 56.3, 55.4, 48.0, 37.4, 20.7, 18.3, 17.8, 16.6. 258 IR (thin HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.56 (s, film) 3377, [M + H]⁺ calcd for 1H), 8.34 (d, J = 5.5 Hz, 1H), 7.32- 2980, 2938, C₂₂H₂₇N₂O₆, 7.27 (m, 2H), 7.24-7.16 (m, 3H), 7.01 1770, 1732, 415.1864; found, (d, J = 5.5 Hz, 1H), 5.09 (dq, J = 7.7, 1674, 1507, 415.1859 6.3 Hz, 1H), 4.77-4.67 (m, 1H), 3.91 1310, 1198, (s, 3H), 2.96-2.86 (m, 1H), 2.41 (s, 1174, 702 3H), 1.49 (d, J = 12 Hz, 3H), 1.30 (d, cm⁻¹ J = 7.0 Hz, 3H), 1.10 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 172.3, 169.0, 162.4, 159.4, 146.7, 143.0, 141.5, 137.5, 128.4, 127.8, 126.7, 109.7, 76.3, 56.3, 48.1, 45.0, 20.8, 18.7, 18.2, 17.3. 259 IR (thin HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.56 (s, film) 3380, [M + H]⁺ calcd for 1H), 8.34 (d, J = 5.4 Hz, 1H), 7.01 (d, 2980, 2938, C₂₁H₂₇N₂O₆S, J = 5.5 Hz, 1H), 6.61 (d, J = 3.5 Hz, 1H), 1770, 1734, 435.1584; found, 6.56 (dq, J = 3.4, 1.1 Hz, 1H), 5.07- 1674, 1506, 435.1581 4.98 (m, 1H), 4.77-4.67 (m, 1H), 3.91 1193, 1173, (s, 3H), 3.20-3.11 (m, 1H), 2.42 (d, 1060, 800 J = 1.1 Hz, 3H), 2.40 (s, 3H), 1.49 (d, cm⁻¹ J = 7.2 Hz, 3H), 1.32 (d, J = 7.0 Hz, 3H), 1.17 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 172.2, 169.0, 162.4, 159.4, 146.7, 143.5, 141.5, 138.0, 137.5, 124.5, 124.1, 109.7, 75.9, 56.3, 48.1, 40.2, 20.8, 18.7, 18.0, 17.3, 15.3. 260 IR (thin HRMS-ESI (wz) ¹H NMR (500 MHz, CDCl₃) δ 8.54 (s, film) 3381, [M + H]⁺ calcd for 1H), 8.35 (d, J = 5.4 Hz, 1H), 7.14- 2980, 2940, C₂₃H₂₈FN₂O₇, 7.06 (m, 1H), 7.01 (d, J = 5.5 Hz, 1H), 1770, 1733, 463.1875; found, 6.62-6.51 (m, 2H), 5.18-5.08 (m, 1675, 1502, 463.1874 1H), 4.72-4.62 (m, 1H), 3.92 (s, 3H), 1193, 1175, 3.79 (s, 3H), 3.42-3.31 (m, 1H), 2.41 1150, 731 (s, 3H), 1.46 (d, J = 7.2 Hz, 3H), 1.23 cm⁻¹ (d, J = 7.1 Hz, 3H), 1.13 (d, J = 6.3 Hz, 3H). ¹⁹F NMR (471 MHz, CDCl₃) δ −13.9-−14.0 (m). 261 IR (thin HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.61 (d, film) 2978, [M + H]⁺ calcd for J = 5.3 Hz, 1H), 7.24-7.17 (m, 2H), 2942, 1769, C₂₁H₂₃N₂O₆, 7.17-7.06 (m, 4H), 5.61 (q, J = 7.1 1712, 1602, 399.1551; found, Hz, 1H), 5.16-5.06 (m, 1H), 4.06 (s, 1501, 1371, 399.1549 3H), 2.93-2.83 (m, 1H), 1.70 (d, J = 1242, 1081, 7.1 Hz, 3H), 1.27 (d, J = 7.1 Hz, 3H), 702 cm⁻¹ 1.04 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 168.2, 158.7, 154.2, 149.1, 145.8, 142.5, 141.6, 131.5, 128.2, 128.0, 126.5, 111.2, 76.5, 56.8, 51.6, 44.7, 17.5, 17.2, 14.0. 262 IR (thin HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.60 (d, film) 2942, [M + H]⁺ calcd for J = 5.2 Hz, 1H), 7.13 (d, J = 5.3 Hz, 1769, 1713, C₂₂H₂₄FN₂O₇, 1H), 7.02 (dd, J = 8.5, 6.7 Hz, 1H), 1602, 1501, 447.1562; found, 6.59-6.50 (m, 2H), 5.56 (q, J = 7.1 1371, 1242, 447.1566 Hz, 1H), 5.15-5.06 (m, 1H), 4.05 (s, 1080, 731 3H), 3.79 (s, 3H), 3.31-3.20 (m, 1H), cm⁻¹ 1.68 (d, J = 7.0 Hz, 3H), 1.18 (d, J = 7.0 Hz, 3H), 1.16 (d, J = 6.3 Hz, 3H). ¹⁹FNMR(471 MHz, CDCl₃) δ −113.9. 263 ESIMS m/z 427.2 ¹H NMR (400 MHz, CDCl₃) δ 8.55 (d, [(M + H)+] J = 7.8 Hz, 1H), 8.35 (dd, J = 5.4, 2.9 Hz, 1H), 7.23-7.05 (m, 4H), 7.01 (dd, J = 5.5, 2.2 Hz, 1H), 5.15 (dq, J = 8.7, 6.2 Hz, 1H), 4.80-4.62 (m, 1H), 3.91 (d, J = 1.7 Hz, 3H), 3.35-3.02 (m, 1H), 2.41 (d, J = 1.8 Hz, 3H), 2.35 (s, 3H), 1.50 (t, J = 6.8 Hz, 3H), 1.25 (dd, J = 6.9, 4.3 Hz, 3H), 1.11 (t, J = 5.9 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 172.39, 168.89, 159.49, 146.67, 141.80, 137.54, 135.55, 130.49, 126.39, 126.30, 126.23, 109.75, 56.28, 48.19, 48.09, 39.75, 20.74, 19.96, 18.56, 18.48, 18.25, 17.58, 17.46, −0.01. 264 ESIMS m/z 429.3 ¹H NMR (400 MHz, CDCl₃) δ 8.55 (d, [(M + H)+] J = 7.6 Hz, 1H), 8.34 (d, J = 5.4 Hz, 1H), 7.23-6.93 (m, 5H), 5.14 (dq, J = 8.4, 6.2 Hz, 1H), 4.73 (p, J = 7.2 Hz, 1H), 3.91 (s, 3H), 3.19 (dq, J = 8.4, 6.9 Hz, 1H), 2.40 (s, 3H), 2.35 (s, 3H), 1.51 (d, J = 7.1 Hz, 3H), 1.25 (d, J = 6.9 Hz, 3H), 1.12 (d, J = 6.2 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 172.39, 168.89, 162.39, 159.48, 146.67, 141.81, 141.66, 137.54, 135.51, 130.50, 126.39, 126.27, 126.26, 109.74, 56.27, 48.19, 39.81, 20.74, 19.94, 18.73, 18.48, 17.46. 265 ESIMS m/z 457.5 ¹H NMR. (400 MHz, CDCl₃) δ 8.49 (s, [(M + H)+] 1H), 8.34 (dd, J = 5.4, 2.9 Hz, 1H), 7.22-7.06 (m, 4H), 6.99 (d, J = 5.4 Hz, 1H), 5.24-5.04 (m, 1H), 4.79- 4.64 (m, 1H), 3.89 (d, J = 1.7 Hz, 3H), 3.18 (dq, J = 9.2, 6.9 Hz, 1H), 2.96 (p, J = 7.0 Hz, 1H), 2.35 (s, 3H), 1.49 (dd, J = 7.2, 5.9 Hz, 3H), 1.37 (dd, J = 7.0, 1.7 Hz, 6H), 1.30-1.18 (m, 3H), 1.11 (t, J = 6.2 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 174.68, 172.48, 162.41, 159.47, 146.56, 142.03, 141.83, 137.71, 135.55, 130.48, 126.40, 126.29, 126.21, 109.59, 56.28, 48.07, 39.77, 33.97, 19.96, 18.81, 18.56, 18.26, 17.60, −0.01. 266 ESIMS m/z 457.4 ¹H NMR (400 MHz, CDCl₃) δ 8.49 (s, [(M + H)+] 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.23- 7.05 (m, 4H), 6.99 (d, J = 5.5 Hz, 1H), 5.12 (dt, J = 8.4, 6.2 Hz, 1H), 4.73(p, J = 7.2 Hz, 1H), 3.89 (s, 3H), 3.38-3.09 (m, 1H), 2.95 (p, J = 7.0 Hz, 1H), 2.35 (s, 3H), 1.50 (d, J = 7.1 Hz, 3H), 1.36 (dd, J = 7.0, 1.1 Hz, 6H), 1.25 (d, J = 6.9 Hz, 3H), 1.12 (d, J = 6.2 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 172.48, 162.36, 159.46, 146.56, 142.03, 141.84, 137.70, 135.51, 130.49, 126.40, 126.27, 126.24, 109.58, 56.28, 48.17, 39.81, 33.96, 19.94, 18.81, 18.76, 18.48, 17.45. 267 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 12.93 film) 3087, [M + H]⁺ calcd for (s, 1H), 10.74 (d, J = 7.6 Hz, 1H), 8.00 2984, 1737, C₂₁H₂₄F₃N₂O₄S, (d, J = 5.1 Hz, 1H), 7.73-7.59 (m, 1513, 1484, 457.1403; found, 1H), 7.51 (t, J = 7.7 Hz, 1H), 7.43 (d, 1311, 1151, 457.1399 J = 7.8 Hz, 1H), 7.33 (t, J = 7.5 Hz, 1H), 1118, 800, 6.89 (d, J = 5.1 Hz, 1H), 5.30-5.18 771 cm⁻¹ (m, 1H), 5.14 (p, J = 7.2 Hz, 1H), 3.96 (s, 3H), 3.37 (p, J = 6.8 Hz, 1H), 1.69 (dd, J = 7.2, 3.2 Hz, 3H), 1.30 (d, J = 6.8 Hz, 3H), 1.14 (d, J = 6.3 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −58.23. 268 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 12.91 film) 3086, [M + H]⁺ calcd for (s, 1H), 10.72 (d, J = 7.7 Hz, 1H), 8.00 2984, 1735, C₂₁H₂₃F₄N₂O₄S, (d, J = 5.1 Hz, 1H), 7.41 (dd, J = 8.7, 1512, 1313, 475.1309; found, 5.3 Hz, 1H), 7.36 (dd, J = 9.1, 2.8 Hz, 1279, 1153, 475.1308 1H), 7.22 (td, J = 8.2, 2.8 Hz, 1H), 6.90 1120, 909, (d, J = 5.1 Hz, 1H), 5.16 (dp, J = 21.6, 730 cm⁻¹ 6.9 Hz, 2H), 3.96 (s, 3H), 3.34 (p, J = 7.2 Hz, 1H), 1.68 (d, J = 7.2 Hz, 3H), 1.29 (d, J = 6.8 Hz, 3H), 1.14 (d, J = 6.3 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −58.77, −113.84. 269 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 12.94 film) 3128, [M + H]⁺ calcd for (d, J = 1.8 Hz, 1H), 10.76 (d, J = 7.9 2947, 1735, C₁₉H₂₉N₂O₄S, Hz, 1H), 7.98 (dd, J = 5.1, 1.4 Hz, 1H), 1511, 1479, 381.1843; found, 6.88 (d, J = 5.1 Hz, 1H), 5.19-5.00 1280, 1200, 381.1840 (m, 2H), 3.95 (s, 3H), 1.85-1.69 (m, 1151, 985, 2H), 1.68-1.32 (m, 7H), 1.30-1.20 797 cm⁻¹ (m, 4H), 1.20-1.01 (m, 3H), 0.96 (d, J = 6.8 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 188.94, 171.20, 157.16, 149.30, 138.96, 131.63, 109.05, 75.08, 56.26, 52.28, 43.32, 43.13, 31.22, 30.75, 25.15, 24.98, 17.81, 17.23, 12.49. 270 HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 9.96 (d, [M + H]⁺ calcd for J = 7.3 Hz, 1H), 8.34 (d, J = 5.5 Hz, C₂₃H₂₆F₃N₂O₅S, 1H), 7.71-7.59 (m, 1H), 7.59-7.47 499.1509; found, (m, 1H), 7.44 (d, J = 7.8 Hz, 1H), 7.39- 499.1508 7.28 (m, 1H), 7.00 (d, J = 5.5 Hz, 1H), 5.28-5.15 (m, 2H), 3.91 (s, 3H), 3.42-3.29 (m, 1H), 2.37 (s, 3H), 1.64 (d, J = 7.2 Hz, 3H), 1.30 (d, J = 6.8 Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −58.23. 271 HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 9.95 (d, [M + H]⁺ calcd for J = 7.3 Hz, 1H), 8.34 (d, J = 5.4 Hz, C₂₃H₂₅F₄N₂O₅S, 1H), 7.42 (dd, J = 8.8, 5.3 Hz, 1H), 517.1415; found, 7.35 (dd, J = 9.2, 2.8 Hz, 1H), 7.22 (td, 517.1410 J = 8.2, 2.8 Hz, 1H), 7.00 (d, J = 5.5 Hz, 1H), 5.35-5.03 (m, 2H), 3.91 (s, 3H), 3.41-3.21 (m, 1H), 2.37 (s, 3H), 1.64 (d, J = 7.1 Hz, 3H), 1.29 (d, J = 6.8 Hz, 3H), 1.13 (d, J = 6.3 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −58.78, −113.98. 272 HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 10.00 [M + H]⁺ calcd for (d, J = 7.3 Hz, 1H), 8.33 (d, J = 5.4 Hz, C₂₁H₃₁N₂O₅S, 1H), 6.99 (d, J = 5.4 Hz, 1H), 5.24- 423.1948; found, 5.06 (m, 2H), 3.91 (s, 3H), 2.36 (s, 423.1944 3H), 1.83-1.71 (m, 3H), 1.71-1.54 (m, 6H), 1.50 (dtd, J = 14.3, 8.0, 3.3 Hz, 1H), 1.39 (dqd, J = 9.7, 6.9, 3.0 Hz, 1H), 1.25 (d, J = 6.5 Hz, 3H), 1.20- 1.02 (m, 2H), 0.96 (dd, J = 6.9, 1.7 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 189.09, 171.67, 168.57, 159.84, 146.29, 145.12, 136.88, 109.21, 74.86, 56.41, 53.04, 43.36, 43.13, 31.22, 30.75, 25.17, 24.99, 21.27, 17.86, 17.08, 12.46. 273 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 14.35 film) 2984, [M + H]⁺ calcd for (s, 1H), 12.85 (d, J = 6.8 Hz, 1H), 7.91 1739, 1571, C₂₁H₂₄F₃N₂O₆, (d, J = 7.1 Hz, 1H), 7.64 (dd, J = 7.9, 1480, 1310, 457.1581; found, 1.4 Hz, 1H), 7.51 (td, J = 1.6, 1.3 Hz, 1150, 1117, 457.1583 1H), 7.44 (d, J = 7.8 Hz, 1H), 7.32 (t, 759 cm⁻¹ J = 7.6 Hz, 1H), 6.79 (d, J = 7.2 Hz, 1H), 5.28-5.14 (m, 1H), 4.73 (p, J = 7.1 Hz, 1H), 3.97 (s, 3H), 3.35 (tt, J = 7.5, 3.8 Hz, 1H), 1.62 (d, J = 7.2 Hz, 3H), 1.29 (d, J = 6.8 Hz, 3H), 1.10 (d, J = 6.2 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −58.22. 274 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 14.33 film) 2985, [M + H]⁺ calcd for (s, 1H), 12.85 (d, J = 6.9 Hz, 1H), 7.91 1739, 1480, C₂₁H₂₃F₄N₂O₆, (d, J = 7.2 Hz, 1H), 7.44 (dd, J = 8.8, 1313, 1153, 475.1487; found, 5.4 Hz, 1H), 7.35 (dd, J = 9.2, 2.8 Hz, 1123, 909, 475.1492 1H), 7.21 (td, J = 8.2, 2.8 Hz, 1H), 6.80 738 cm⁻¹ (d, J = 7.2 Hz, 1H), 5.23-5.09 (m, 1H), 4.73 (p, J = 7.2 Hz, 1H), 3.98 (s, 3H), 3.41-3.25 (m, 1H), 1.61 (d, J = 7.2 Hz, 3H), 1.27 (d, J = 6.8 Hz, 3H), 1.11 (d, J = 6.3 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −58.77, −114.03. 275 IR (thin HRMS-ESI (m/z) ¹H NMR (400 MHz, CDCl₃) δ 14.40 film) 2945, [M + H]⁺ calcd for (s, 1H), 12.75 (d, J = 7.1 Hz, 1H), 7.91 1733, 1569, C₁₉H₂₉N₂O₆, (d, J = 7.2 Hz, 1H), 6.79 (d, J = 7.2 Hz, 1479, 1300, 381.2020; found, 1H), 5.10 (qd, J = 6.4, 3.0 Hz, 1H), 1212, 1152, 381.2016 4.78-4.63 (m, 1H), 3.97 (s, 3H), 1.85- 1029, 757 1.68 (m, 2H), 1.68-1.51 (m, 7H), cm⁻¹ 1.51-1.44 (m, 1H), 1.44-1.33 (m, 1H), 1.24 (d, J = 6.4 Hz, 3H), 1.18- 0.99 (m, 2H), 0.94 (d, J = 6.9 Hz, 3H). 276 IR (thin HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 14.39 film) 2978, [M + H]⁺ calcd for (s, 1H), 12.82 (d, J = 6.9 Hz, 1H), 7.89 2937, 1735, C₂₀H₂₅N₂O₆, (d, J = 7.2 Hz, 1H), 7.32-7.25 (m, 1643, 1569, 389.1707; found, 2H), 7.25-7.15 (m, 3H), 6.78 (d, J = 1479, 1452, 389.1703 7.2 Hz 1H), 5.10 (dq, J = 8.1, 6.3 Hz, 1211, 1154, 1H), 4.75-4.64 (m, 1H), 3.97 (s, 3H), 729, 702 2.96-2.86 (m, 1H), 1.56 (d, J = 7.2 cm⁻¹ Hz, 3H), 1.30 (d, J = 6.9 Hz, 3H), 1.12 (d, J = 6.2 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 171.1, 165.5, 152.5, 149.3, 143.0, 131.0, 128.4, 127.8, 126.7, 123.7, 107.6, 76.5, 56.5, 48.9, 45.0, 18.2, 17.9, 17.4. 277 IR (thin HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 14.42 film) 2978, [M + H]⁺ calcd for (s, 1H), 12.80 (d, J = 7.1 Hz, 1H), 7.89 2939, 1735, C₂₁H₂₆FN₂O₇, (d, J = 7.2 Hz, 1H), 7.11 (dd, J = 8.4, 1570, 1502, 437.1719; found, 6.7 Hz, 1H), 6.78 (d, J = 7.1 Hz, 1H), 1453, 1213, 437.1727 6.63-6.55 (m, 2H), 5.22-5.13 (m, 1152, 1031, 1H), 4.72-4.61 (m, 1H), 3.98 (s, 3H), 952, 731 3.80 (s, 3H), 3.38-3.29 (m, 1H), 1.51 cm⁻¹ (d, J = 7.2 Hz, 3H), 1.25 (d, J = 7.1 Hz, 3H), 1.13 (d, J = 6.3 Hz, 3H). ¹⁹F NMR (471 MHz, CDCl₃) δ −113.9 (dt, J = 11.2, 7.3 Hz). 278 87-88 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.53 (d, [M + H]⁺ calcd for J = 7.1 Hz, 1H), 8.34 (d, J = 5.4 Hz, 1H), C₂₄H₃₀N₂O₆, 7.22-7.06 (m, 4H), 7.00 (d, J = 5.5 Hz, 443.2177; found, 1H), 5.14 (dq, J = 8.4, 6.3 Hz, 1H), 4.78- 443.2186 4.68 (m, 1H), 3.90 (s, 3H), 3.18 (dt, J = 8.4, 6.9 Hz, 1H), 2.74 (q, J = 7.5 Hz, 2H), 2.35 (s, 3H), 1.51 (d, J = 7.1 Hz, 3H), 1.28 (t, J = 7.5 Hz, 3H), 1.25 (d, J = 6.9 Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 172.43, 172.35, 162.39, 159.50, 146.60, 141.81, 141.71, 137.61, 135.51, 130.49, 126.38, 126.27, 109.70, 76.30, 56.28, 48.16, 39.78, 30.93, 27.28, 19.97, 18.77, 18.49, 17.47, 8.81. 279 88-91 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.52 (d, [M + H]⁺ calcd for J = 6.1 Hz, 1H), 8.33 (d, J = 5.4 Hz, 1H), C₂₅H₃₂N₂O₆, 7.21-7.06 (m, 4H), 6.99 (d, J = 5.5 Hz, 457.2333; found, 1H), 5.14 (dq, J = 8.4, 6.2 Hz, 1H), 4.77- 457.2343 4.69 (m, 1H), 3.89 (s, 3H), 3.18 (dq, J = 8.4, 6.9 Hz, 1H), 2.68 (t, J = 7.5 Hz, 2H), 2.35 (s, 3H), 1.82 (h, J = 7.4 Hz, 2H), 1.50 (d, J = 7.1 Hz, 3H), 1.25 (d, J = 6.8 Hz, 3H), 1.12 (d, J = 6.2 Hz, 3H), 1.05 (t, J = 7.4 Hz, 3H). ¹³C NMR (126 MHz, CDCl₃) δ 172.43, 171.45, 162.37, 159.46, 146.60, 141.81, 141.76, 137.58, 135.51, 130.49, 126.38, 126.27, 109.67, 76.28, 56.25, 48.15, 39.77, 35.79, 19.96, 18.77, 18.48, 18.15, 17.46, 13.60. 280 ESIMS m/z 471 ¹H NMR (400 MHz, CDCl₃) δ 8.53 (s, ([M + H]⁺) 1H), 8.34 (d, J = 5.4 Hz, 1H), 7.22- 7.06 (m, 4H), 7.00 (d, J = 5.5 Hz, 1H), 5.13 (dq, J = 8.3, 6.2 Hz, 1H), 4.85- 4.67 (m, 1H), 3.90 (s, 3H), 3.18 (dq, J = 8.4, 6.9 Hz, 1H), 2.80-2.67 (m, 2H), 2.35 (s, 3H), 1.77 (p, J = 7.6 Hz, 2H), 1.48 (dd, J = 17.8, 7.4 Hz, 5H), 1.25 (d, J = 6.9 Hz, 3H), 1.12 (d, J = 6.2 Hz, 3H), 0.96 (t, J = 7.4 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 172.46, 171.62, 162.40, 159.50, 146.61, 141.84, 141.82, 137.63, 135.53, 130.51, 126.41, 126.29, 126.27, 109.68, 56.26, 48.17, 39.80, 33.67, 26.64, 22.22, 19.96, 18.77, 18.49, 17.47, 13.77. 281 ESIMS m/z 455.4 ¹H NMR (400 MHz, CDCl₃) δ 8.52 (d, ([M + H]⁺) J = 8.0 Hz, 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.22-7.05 (m, 4H), 6.99 (d, J = 5.5 Hz, 1H), 5.13 (dq, J = 8.3, 6.2 Hz, 1H), 4.82- 4.68 (m, 1H), 3.90 (s, 3H), 3.19 (dq, J = 8.4, 6.9 Hz, 1H), 2.35 (s, 3H), 1.97 (tt, J = 8.0, 4.6 Hz, 1H), 1.51 (d, J = 7.2 Hz, 3H), 1.32-1.21 (m, 5H), 1.12 (d, J = 6.3 Hz, 3H), 1.07 (dq, J = 7.5, 4.0 Hz, 2H). ¹³C NMR (101 MHz, CDCl₃) δ 172.49, 172.45, 162.36, 159.53, 146.61, 142.00, 141.84, 137.50, 135.52, 130.51, 126.41, 126.29, 126.26, 109.67, 60.39, 56.31, 48.13, 39.80, 21.04, 19.96, 18.83, 18.49, 17.47, 14.21, 13.03, 9.26. 282 ESIMS m/z 491.4 ¹H NMR (400 MHz, CDCl₃) δ 8.56 (d, ([M + H]⁺) J = 7.9 Hz, 1H), 8.40 (d, J = 5.5 Hz, 1H), 8.32-8.17 (m, 2H), 7.67-7.57 (m, 1H), 7.50 (dd, J = 8.3, 7.0 Hz, 2H), 7.20- 7.08 (m, 4H), 7.06 (d, J = 5.5 Hz, 1H), 5.11 (dq, J = 8.2, 6.2 Hz, 1H), 4.89- 4.55 (m, 1H), 3.90 (s, 3H), 3.23-3.03 (m, 1H), 2.34 (s, 3H), 1.47 (d, J = 7.2 Hz, 3H), 1.23 (d, J = 6.9 Hz, 3H), 1.08 (d, J = 6.2 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 172.51, 164.53, 162.25, 159.68, 146.82, 141.85, 135.53, 133.47, 130.60, 130.50, 129.20, 128.55, 126.40, 126.28, 126.25, 109.77, 56.33, 48.08, 39.79, 19.95, 18.84, 18.47, 17.46. 284 HRMS-ESI (m/z) ¹H NMR (500 MHz, CDCl₃) δ 8.43 (d, [M + H]⁺ calcd for J = 7.8 Hz, 1H), 8.28 (d, J = 5.3 Hz, 1H), C₂₆H₃₄N₂O₇, 7.22-7.05 (m, 4H), 6.94 (d, J = 5.4 Hz, 487.2439; found, 1H), 5.78 (q, J = 6.4 Hz, 2H), 5.15 (dq, 487.2450 J = 8.5, 6.3 Hz, 1H), 4.75 (p, J = 7.2 Hz, 1H), 3.89 (s, 3H), 3.25-3.15 (m, 1H), 2.55 (p, J = 7.0 Hz, 1H), 2.35 (s, 3H), 1.53 (d, J = 7.2 Hz, 3H), 1.26 (dd, J = 7.1, 5.9 Hz, 3H), 1.14 (dd, J = 8.7, 6.6 Hz, 9H). ¹³C NMR (126 MHz, CDCl₃) δ 176.26, 172.52, 162.94, 160.27, 145.58, 144.25, 142.19, 141.80, 135.51, 130.50, 126.37, 126.26, 109.50, 89.96, 76.30, 56.13, 48.38, 39.79, 33.86, 19.96, 18.69, 18.62, 18.51, 17.51. 285 ESIMS m/z 413 ¹H NMR (400 MHz, CDCl₃) δ 8.60 (d, ([M + H]⁺) J = 5.3 Hz, 1H), 7.18 (d, J = 5.4 Hz, 1H), 7.14 (dd, J = 3.8, 1.4 Hz, 2H), 7.08- 6.99 (m, 2H), 5.60 (q, J = 7.1 Hz, 1H), 5.18 (dq, J = 8.2, 6.2 Hz, 1H), 4.06 (s, 3H), 3.14 (dq, J = 8.3, 6.9 Hz, 1H), 2.29 (s, 3H), 1.71 (d, J = 7.0 Hz, 3H), 1.22 (d, J = 6.9 Hz, 3H), 1.07 (d, J = 6.3 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 168.34, 158.73, 154.19, 149.12, 145.79, 141.65, 141.53, 135.54, 131.44, 130.30, 126.41, 126.23, 126.11, 111.45, 56.84, 51.51, 39.55, 20.00, 17.74, 17.71, 14.03. *Cmpd. No.—Compound Number

TABLE 3 Biological Testing Rating Scale Rating Table for Fungal Pathogens % Control Rating  >80 A ≤80 B Not Tested C  ≤0 D

TABLE 4 Biological Activity - PUCCRT and SEPTTR Disease Control in High Volume Applications HV activity at 100 ppm* *PUCCRT *SEPTTR *Cmpd. No. 1DP* 3DC* 1DP* 3DC* 116 A A B A 117 B B B B 118 A A D B 119 A B D B 120 B B D B 121 A A D B 122 A A B B 123 A B D B 124 B D D B 125 B D D B 126 A B D B 127 B B D B 128 A A A A 129 A B B B 130 A A B B 131 A A B B 132 A A A B 133 A B B B 134 B B B B 135 B B B B 136 A B B B 137 A B B B 138 A A A B 139 B D B B 140 A B B B 141 A B A B 142 A A A B 143 A D B B 144 D B B B 145 B B B B 146 A B A B 147 A B A B 148 A B A B 149 D D B B 150 D B B B 151 B D B B 152 A B B B 153 B B B B 154 D D B B 155 B B B B 156 D B B B 157 B D B B 158 A A A B 159 A A A A 160 B A B B 161 D D B B 162 D D B B 163 B B B B 164 A A B A 165 A A A A 166 A A A A 167 A A A A 168 A A B A 169 A A A A 170 A A B B 171 A A B B 172 B A B B 173 A B B B 175 A A B B 176 A B D B 258 A A B B 259 A A B D 260 A B B B 267 A B B B 268 A B B B 269 B A B B 276 A B B B 277 B D B B *Cmpd. No.—Compound Number *PUCCRT—Wheat Brown Rust (Puccinia triticina) *SEPTTR—Wheat Leaf Blotch (Zymoseptoria tritici) *1DP—1 Day Protectant *3DC—3 Day Curative *ppm—Parts Per Million

TABLE 5 Biological Activity - PUCCRT and SEPTTR Disease Control in Low Volume Applications LV activity at 121.5 g/ha* *PUCCRT *SEPTTR *Cmpd No. 1DP* 3DC* 1DP* 3DC* 177 A A A A 178 B B B B 179 A A B B 180 B B B B 234 B B B B 235 B B A A 236 B B B D 237 B B B B 238 A B A A 239 D D B B 240 D D B B 241 D D B D 242 A B A A 243 B B B B 244 A B A A 245 A B A A 246 A A A A 247 B B B B 248 A B B A 249 A A A A 250 D B B B 251 B B B B 252 D B D B 253 A B B B 254 A A A A 255 A B B A 256 A A A A 257 B B B B 258 B A B A 259 B D B D 260 D D B D 261 B D B D 262 D D B B 263 B B B B 264 A A B B 265 B B B B 266 B B B B 275 B D D D 231 A B B B 232 A B D B 233 A B B B 270 B B B B 271 B B B B 272 B B B B 273 B B B B 274 B B B B 276 B B B B 277 D B B B *Cmpd. No.—Compound Number *PUCCRT—Wheat Brown Rust (Puccinia triticina) *SEPTTR—Wheat Leaf Blotch (Zymoseptoria tritici) *1DP—1 Day Protectant *3DC—3 Day Curative *g/ha—grams per hectare

TABLE 6 Biological Activity - High Volume Disease Control at 25 ppm PHAKPA* *Cmpd. No. 1DP* 3DC* 128 C A 158 C B 159 C A 175 A A 177 A A 178 A B 179 A A 180 A B 181 B D 182 B B 183 A B 184 A A 185 D D 186 B B 187 A D 188 A B 189 A B 190 D D 191 B B 192 B D 193 B D 194 D D 195 B D 196 A B 197 D D 198 D D 199 D D 200 B B 201 B B 202 B D 203 A B 204 A A 205 A B 206 B D 207 B D 208 A D 209 A A 210 D D 211 B D 212 B B 213 A B 214 B B 215 B B 216 B D 217 B D 218 D B 219 D D 220 B B 221 D D 222 D D 223 D D 224 B D 225 D D 226 D B 227 B D 228 D D 229 D D 230 D D 231 B D 232 B D 233 A B 234 A A 235 A A 236 A D 237 A A 238 A A 239 B B 240 B B 241 D D 242 A A 243 A A 244 A A 245 A A 246 A A 247 A B 248 A A 249 A A 250 B B 251 A B 252 B B 253 A A 254 A A 255 A A 256 A A 257 B D 258 A A 259 B B 260 A B 261 B B 262 B B 263 A B 264 A A 265 A A 266 A A 270 A B 271 A A 272 A B 273 B B 274 B B 275 B B 276 D B 277 B B 284 A A 278 A A 279 A A 280 A A 281 A A 282 A A 285 A A *Cmpd. No.—Compound Number *PHAKPA—Asian Soybean Rust (Phakopsora pachyrhizi) *1DP—1 Day Protectant *3DC—3 Day Curative

TABLE 7 Biological Activity - Disease Control in 1DP* test at 100 ppm Cmpd. No.* ALTESO* CERCBE* COLLLA* LEPTNO* 263 B B D B 264 B A B A 266 B B D A *Cmpd. No.—Compound Number *ALTESO—Tomato Early Blight (Alternaria solani) *CERCBE—Leaf Spot of Sugar Beets (Cercospora beticola) *COLLLA—Cucumber Anthracnose (Glomerella lagenarium; Anamorph: Colletotricum lagenarium) *LEPTNO—Wheat Glume Blotch (Parastagonospora nodorum)

TABLE 8 Biological Activity - Disease Control in 1DP* Test at 100 ppm Cmpd. No.* PSPECU* PYRIOR* RHYNSE* UNCINE* 263 B B B A 264 B A B A 266 D A B A *Cmpd. No.—Compound Number *PSPECU—Cucumber Downy Mildew (Pseudoperonospora cubensis) *PYRIOR—Rice Blast (Magnaporthe grisea; Anamorph: Pyricularia oryzae) *RHYNSE—Barley Scald (Rhyncosporium secalis) *UNCINE—Grape Powdery Mildew (Uncinula necator) *1DP—1 Day Protectant 

What is claimed is:
 1. A compound of Formula I

wherein: Q is

X is hydrogen or C(O)R₄; Y is hydrogen or C(O)R₄; Z is N or N⁺→O⁻ and W is O or S; R₁ is hydrogen or alkyl, substituted with 0, 1 or multiple R₇; R₂ is methyl; R₃ is alkyl, aryl or heteroaryl, each optionally substituted with 0, 1 or multiple R₇; R₄ is alkoxy or benzyloxy, each optionally substituted with 0, 1, or multiple R₇; R₅ is hydrogen, alkoxy, or halo, each optionally substituted with 0, 1, or multiple R₇; R₆ is hydrogen, —C(O)R₈, or —CH₂OC(O)R₈; R₇ is hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkynyl, alkoxy, cyano, or heterocyclyl, each optionally substituted with 0, 1, or multiple R₉, R₈ is alkyl, alkoxy, or aryl, each optionally substituted with 0, 1, or multiple R₇; R₉ is hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkoxy, or heterocyclyl; and R₁₀ is hydrogen or alkyl, each substituted with 0, 1 or multiple R₇.
 2. The compound according to claim 1, wherein Q is

and X and Y are hydrogen.
 3. The compound according to claim 2, wherein R₁ and R₁₀ are independently chosen from hydrogen or alkyl.
 4. The compound according to claim 2, wherein R₃ is aryl, optionally substituted with 0, 1 or multiple R₇.
 5. The compound according to claim 2, wherein R₁ and R₁₀ are independently chosen from hydrogen or alkyl, and R₃ is aryl, optionally substituted with 0, 1 or multiple R₇.
 6. The compound according to claim 1, wherein Q is

and X is C(O)R₄ and Y is hydrogen.
 7. The compound according to claim 6, wherein R₁ and R₁₀ are independently chosen from hydrogen or alkyl.
 8. The compound according to claim 6, wherein R₃ is aryl, optionally substituted with 0, 1 or multiple R₇.
 9. The compound according to claim 6, wherein R₁ and R₁₀ are independently chosen from hydrogen or alkyl, and R₃ is aryl, optionally substituted with 0, 1 or multiple R₇.
 10. The compound according to claim 1, wherein Q is

wherein X is hydrogen.
 11. The compound according to claim 10 wherein Z is N.
 12. The compound according to claim 11 wherein W is O.
 13. The compound according to claim 12, wherein R₅ is alkoxy.
 14. The compound according to claim 13, wherein R₆ is hydrogen.
 15. The compound according to claim 14, wherein R₁ and R₁₀ are independently chosen from hydrogen or alkyl.
 16. The compound according to claim 14, wherein R₃ is aryl, optionally substituted with 0, 1 or multiple R₇.
 17. The compound according to claim 14, wherein R₁ and R₁₀ are independently chosen from hydrogen or alkyl, and R₃ is aryl, optionally substituted with 0, 1 or multiple R₇.
 18. The compound according to claim 13, wherein R₆ is chosen from —C(O)R₈ or —CH₂OC(O)R₈.
 19. The compound according to claim 18, wherein R₁ and R₁₀ are independently chosen from hydrogen or alkyl.
 20. The compound according to claim 18, wherein R₃ is aryl, optionally substituted with 0, 1 or multiple R₇.
 21. The compound according to claim 18, wherein R₁ and R₁₀ are independently chosen from hydrogen or alkyl, and R₃ is aryl, optionally substituted with 0, 1 or multiple R₇. 